We demonstrate that both exercise and MET have beneficial effects for treating hepatic steatosis in diabetic mice, and that the combined exercise and MET showed greater benefit, mainly through reducing oxidative and ER stress (PERK-eIF2α-ATF4 pathway) and mediated hepatic apoptosis and enhancing the antioxidant defense system via AMPK-Nrf2-HO-1 pathway. Here, EIF2AK3 is linked to fatty liver disease.