Abstract. The present study was designed to investigate the therapeutic effects of bee venom (BV) on high-fat diet (HFD)-induced non-alcoholic fatty liver (NAFL) in rats at different levels. Histological manifestations, hepatic lipid content, liver function tests, glucose homeostasis, lipid abnormalities, adipocytokines, lipid peroxidation, disturbed glutathione and antioxidant enzymes systems and dysregulation of Nrf2 transcription factor were assessed. In the present study, the NAFL rats were subcutaneously treated with BV with different doses (0.01, 0.05, 0.1 mg/kg). The results indicated that BV treatment completely normalized the lipid profile values of NAFL rats. Fasting blood sugar, insulin level and homeostatic model assessment of insulin resistance significantly decreased. BV treated rats showed a significantly lower level of all liver enzymes and bilirubin. Moreover, BV treatment significantly increased the levels of active nuclear erythroid factor 2 like 2, glutathione (GSH) (total and reduced), GSH/glutathione disulphide ratio and activities of glutathione reductase, glutathione-S-transferase and glutathione peroxidase (total and Se-dependent). The level of tumor necrosis factor-α was reduced. Treatment showed correction of adiponectin level, and significant downregulation of hepatic triglycerides and cholesterol. At the histological level, BV improved the architecture of liver cells showing normal sinusoids. It may be concluded that BV may represent an interesting therapeutic alternative for the treatment of NAFL disease.