Abstract: Objective：To compare the curative effects of sitagliptin and glipizide on patients of type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease, and to analyze their effects on blood glucose and liver function. Methods：A total of 112 patients of type 2 diabetes mellitus complicated with nonalcoholic fatty liver in the Third Rehabilitation Hospital in Shanghai from June 2015 to April 2017 were randomized into sitagliptin group (n=56) treated with metformin combined with sitagliptin and glipizide group (n=56) treated with metformin combined with glipizide. The efficacy on fatty liver was compared between two groups, the blood glucose, liver function, blood lipid and insulin resistance index (HOMA-IR) were compared between two groups before and after treatment. Results：The total effective rate was 94.6% (53/56) in sitagliptin group, significantly higher than that in glipizide group (75.0%, 42/56, P<0.05). The blood glucose and blood lipid were significantly improved after treatment in both group, with no significantly difference between two groups . The liver function indexes (AST, ALT, GGT) and HOMA-IR were all significantly improved after treatment in both groups, being significantly better in sitagliptin group compared with those in glipizide group (P<0.05). The overall adverse reaction rate was 19.6% (11/56) in sitagliptin group and 17.9% (10/56) in glipizide group, with no statistical difference. Conclusions：Sitagliptin combined with metformin can improve the therapeutic effect on fatty liver in patients of type 2 diabetes complicated with nonalcoholic fatty liver. Compared with glipizide, sitagliptin can more effectively improve the liver function and HOMA-IR, worthy to be popularized.