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Introduction: Liver steatosis (fatty liver) is frequently found during the conditions such as diabetes and obesity. The current experimental study was executed the effect of adropin against high fat diet (HFD)-induced obese diabetic Wistar rats via nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Materials and Methods: Wistar rats were randomly divided into six groups and divided as follows: normal, HFD control, HFD + adropin (2.5, 5 and 10 mg/kg), and HFD + Glibenclamide (2.5 mg/kg), respectively. Lipid and carbohydrate metabolism, hepatic parameters, antioxidant, and proinflammatory cytokines were estimated at the end of the experimental study. Nrf2 transcription and nuclear level were also estimated. In vitro adropin diminished the accumulation of lipid droplets in dose-dependent manner and no effect was observed on the lipolysis. Type II diabetic rats fed with HFD exhibited a marked reduction in hepatic extraction faction and hepatic steatosis after the adropin and glibenclamide treatment. Results: Adropin significantly (P < 0.001) altered the hepatic parameter such as alanine transaminase, aspartate transaminase, alkaline phosphatase; antioxidant parameters such as thiobarbituric acid reactive substances, 8-OhdG, superoxide dismutase, glutathione (GSH) peroxidase, catalase, GSH, GSH reductase, GSH S-transferase; proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, respectively. In addition, adropin significantly reduced the nuclear Nrf2 activity at dose-dependent manner. Conclusion: Adropin improved insulin sensitivity, reduced lipogenesis in the adipocytes and also decrease the inflammation through downregulated cytokines (Nrf2 pathway). [ABSTRACT FROM AUTHOR]