In this study, we further investigated the changes of hepatic insulin sensitivity and fat synthesis, secretion, and catabolic pathway in obese T2DM rats at two, four, and eight weeks after RYGB; then, we focused on the mechanism of the reduction hepatic lipid toxicity, the improvement of liver insulin resistance, and the inhibition of NAFLD by RYGB. Here, INS is linked to type 2 diabetes mellitus.