Background & Aims: Diabetes mellitus is one of the most common chronic diseases in the world (1). Diabetes and hyperglycemia caused by diabetes lead to disorders in various organs such as lungs, heart, muscles, kidneys, etc. (9, 10). One of the main complications of diabetes is diabetic cardiomyopathy; Diabetic cardiomyopathy is the result of diabetes-induced changes in the structure and function of the heart. Diabetic cardiomyopathy occurs as a result of impaired glucose and lipid metabolism associated with diabetes, which leads to increased oxidative stress and activation of multiple inflammatory pathways that mediate cellular and extracellular damage, pathological remodeling of the heart, and diastolic and systolic dysfunction. Preclinical studies in animal models of diabetes have identified several intracellular pathways involved in the pathogenesis of diabetic cardiomyopathy and potential cardioprotective strategies for disease prevention and treatment, including anti-fibrotic agents, anti-inflammatory agents, and antioxidants (11). Cellular energy homeostasis is a fundamental process that governs the overall health of the cell and is critical for cell survival. Central to this is the control of ATP production and utilization, which is regulated by a myriad of enzymatic reactions controlling cellular metabolism (12). Adenosine monophosphateactivated protein kinase (AMPK) is an energy sensor with aberrant expression in various diseases, including diabetes (12). There is considerable evidence that AMPK is reduced in cardiac tissues of animals and humans with type 2 diabetes or metabolic syndrome compared with non-diabetic controls, and that AMPK stimulation (physiological or pharmacological) can ameliorate diabetesrelated cardiovascular complications (14). Considering the role of AMPK in energy metabolism in the heart, as well as the effects of diabetes and exercise on the gene and protein expression of this energy sensor, measuring the changes of this gene can improve our knowledge about the effect of different adaptations caused by different exercises, as well as the effect of lack of exercise. With the aim of investigating the effect of maintaining these adaptations after training (22, 23). However, so far, no research has been done that specifically compares the effect of two common training methods, continuous and intermittent training, followed by no training on cardiac AMPK gene expression in diabetic rats, which shows the necessity of the current research. According to the mentioned information, the present study was conducted with the aim of comparing the effect of a detraining period followed by aerobic and HIIT exercises on cardiac AMPK gene expression in alloxan-treated diabetic rats. Methods: In this experimental research, 48 male Wistar rats (age: 10-weeks; weigh: 220±20 grams) were randomly divided into six groups (n=8). One group was considered as a healthy control and the rest of the rats were made diabetic using a single dose of 90 mg/kg of alloxan. One group was considered as diabetic control; and the rats were divided into two groups of high-intensity interval training (HIIT) and continuous moderate aerobic training (MICT). After 12 weeks of training, half of the rats in each group were sacrificed; and the rats were sacrificed after 2 weeks of no training. MICT program was performed for 5 sessions per week with a gradual increase in speed (18-26 m/min) and time (10-55 minutes). HIIT program also included 5 30-minute sessions per week in the form of running on a treadmill with one-minute repetitions and 2-minute active rest between each interval. For statistical analysis, one-way analysis of variance and Tukey's post hoc test were used and the significance level (P ≤ 0.05) was considered. Results: The results showed that the induction of diabetes decreased the cardiac AMPK gene expression compared to the healthy control group (P < 0.001), also the results showed that after 12 weeks of training, there was a significant increase in the cardiac AMPK gene expression in the training groups compared to the control group. Diabetes control was observed (P < 0.001), but no significant difference was observed between the two exercise groups (P > 0.05). Also, the results showed that after 2 weeks of non-training, there was a slight decrease in cardiac AMPK gene expression compared to the training groups, and these changes were not significant (P > 0.05). Conclution: The results of the present study showed that induction of diabetes with alloxan decreased cardiac AMPK gene expression, which was related to hyperglycemia caused by induction of diabetes with alloxan injection. Previous research has also shown that a single dose of alloxan injection with 90 mg/kg body weight of rats induces diabetes (24-26). According to the findings of the present study, 12 weeks of continuous aerobic exercise and HIIT both significantly increased cardiac AMPK gene expression in diabetic rats, but no significant difference was observed between the two types of exercise. Based on the research conducted in animal models, exercise increases cardiac AMPK values, which are consistent with the results of the present study (30, 31). However, comparing the effects of continuous and HIIT exercises, the results of these two studies were different from our findings; In their research comparing the effect of moderate intensity continuous training and HIIT training on AMPK of skeletal and cardiac muscle, Wen et al. reported that the effects of HIIT training on increasing oxidative capacity and AMPK are more obvious (30); The results of Su et al.'s research showed better effects of continuous training on AMPK and PGC-1α gene expression in the HIIT group than continuous aerobic training (30). As shown in various animal models and patient studies, physical exercise is known to be cardioprotective and can partially compensate for cardiac damage. At the cellular level, exercise counteracts heart disease-related changes in these cellular pathways and can improve heart function (32). AMPK activation leads to the regulation of metabolism, protein transport, transcription factors and/or activators, kinases, and other enzymes and non-enzymatic proteins. AMPK increases substrate uptake and utilization in the heart, enhances mitochondrial biogenesis, and modulates the activity of specific proteins and transcription factors to exert cardioprotective functions (33). Therefore, exercise training can moderate the effects of diabetes on the heart by increasing cardiac AMPK. AMPK also plays an important role in reducing oxidative stress, regulating autophagy and anti-apoptosis of cardiomyocytes (29, 34). Exercise activates signaling molecules and transcriptional networks to promote physiological adaptations such as mitochondrial biogenesis (35). It has been reported that after swimming exercises in rats, the levels of activated AMPK showed a decrease in cardiac fibrosis due to the inhibition of NADPH oxidase (36). This finding has been confirmed as decreased AMPK activity by beta-adrenergic activation exacerbates cardiac fibrosis (37). These changes are important because exercise activates AMPK and thus may be able to inhibit pathological hypertrophy and cardiac fibrosis (38). Other findings of our research showed that 2 weeks of detraining after exercise decreased AMPK in both exercise groups, but this decrease was not statistically significant. In line with the findings of the current research, Cao et al also reported in their research that after the training period, a significant increase in AMPK level was observed, but after stopping training for 10 days, the AMPK level started to decrease, but the changes were not significant 40). Based on the results, it can be said that any two methods of continuous aerobic exercise and HIIT increase the expression of the AMPK gene; Also, after two weeks ofdetraining, cardiac AMPK gene expression is still high in diabetic rats. However, more research is needed to investigate the longer-term effects of non-exercise on AMPK gene expression and mechanisms related to non-exercise on diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]