Object: We investigated the effects of sodium-glucose co-transporter 2 inhibitor, empagliflozin, on hepatic steatosis in an animal model of type 2 diabetes (T2DM). Methods: Empagliflozin (10 mg/kg, OL-EMPA) or voglibose (0.6 mg/kg, OL-VOG) (n = 10 each) was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats once daily for 12 weeks. Control Long-Evans Tokushima Otsuka (LT) and OLETF (OL-C) rats received saline (n = 10 each). Changes in blood glucose, lipid profile, and liver fat content were measured. Hepatic gene and protein expressions related to gluconeogenesis and lipogenesiswere evaluated by quantitative RT-PCR and western blot analysis. Sirtuin (SIRT1) activity was also measured. Results: After 12 weeks of treatment, blood glucose levels were significantly suppressed in OL-EMPA and OL-VOG groups compared with the OL-C group (P< 0.05). Liver fat content was significantly higher in the OL-C group than in the OL-EMPA and OL-VOG groups.Hepatic gene expressions involved in gluconeogenesis (G6Pase, FBP1, PEPCK) and lipogenesis (ACC, FAS, SREBP-1c)were significantly decreased in the OL-EMPA group compared to other OLETF groups (OL-C, OL-VO). Sirtuin (SIRT1) expression level and SIRT1 activity were markedly reduced in OL-C rats; however, its expression increased in theOL-EMPA and OL-VOG groups. AMPK phosphorylation level was remarkably increased by empagliflozin treatment in OLETF rats compared to other OLETF groups. Conclusion: Long-term empagliflozin and voglibose treatment reduced hepatic steatosis with suppression of gluconeogenesis and lipogenesis pathway in OLETF rats.Wesuggest that this metabolic improvement might be related to SIRT-1 and AMPK pathway in an animal model of T2DM. But empagliflozin is thought to have more advantage to prevent hepatic steatosis than voglibose in T2DM.