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Introduction: Type 2 diabetes mellitus (DM) and Alzheimer's disease (AD) are two major medical conditions that constitute a significant financial burden on most healthcare systems. Due to AD sharing "insulin resistance" mechanistic features with DM, some scientists have proposed "type 3 DM" terminology for it. This study aims to compare the prophylactic effect of exercise and metformin on cognitive brain functions in rats with type 3 DM., Material and Methods: Two groups of rats were included in the study: the control group ( n = 15) and the streptozotocin-induced type 2 diabetic group ( n = 45). The diabetic group was subdivided into three equal subgroups: a sedentary non-treated diabetic group, an exercised group, and a metformin-treated group. We estimated step-down avoidance task latency, serum glucose, insulin, free fatty acids (FFA), cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides (TG), brain Aβ-42 and glucose, histological changes by toluidine blue, and immunohistochemistry for brain Aβ-42 and tau-positive cells., Results: Serum glucose, FFA, TG, cholesterol, LDL, brain Aβ-42, brain glucose, the number of hippocampal dark and degenerated cells, and brain Aβ-42 and tau-positive cells, were all significantly lower. In contrast, serum insulin and HDL, the number of hippocampal granular cells, and latency of the step-down avoidance task were significantly higher in exercised and metformin-treated groups compared to the diabetic group. There were significantly higher values of serum insulin and brain/plasma glucose ratio and number of brain tau-positive cells in the metformin-treated group than in the exercised group., Conclusions: We can conclude that exercise can be as effective as metformin regarding prophylaxis against the deleterious effects of type 3 DM on cognitive brain functions., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)