Objective: To explore the expression of blood serum free fatty acid (FFA) and cytokeratin 18 (CK18) and their impact on patients with type 2 diabetes mellitus with non alcoholic fatty liver disease (NAFLD). Methods: Forty patients with type 2 diabetes, 40 cases with type 2 diabetes with alcoholic fatty liver disease, 20 cases of healthy controls were enrolled. Fasting blood glucose (FPG), cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl (GGT), glycated hemoglobin (HbA1c), insulin (FINS), FFAa and CK18 were detected, and liver B-ultrasound was performed. Results: ① BMI, FPG, FINS, A1C levels and HOMA-IR were significantly higher in group of type 2 diabetes than that of the normal control group; CH, TG, ALT, AST, GGT levels were not significantly different. BMI, FPG, FINS, CH, TG, ALT, AST, GGT levels and HOMA-IR were significantly higher in group of type 2 diabetes with NAFLD than that of type 2 diabetes group (P <0.001); ② Compared with normal control group, FFA levels were significantly increased in group of type 2 diabetes, but CK18 levels were not significantly different. In group of type 2 diabetes with NAFLD, CK18 and FFA levels were higher than normal control group as well as type 2 diabetes group(P < 0.001). Conclusion: Compared with type 2 diabetes patients, insulin resistance, metabolic disorders were more significant and apoptosis of liver cells increased in patients with type 2 diabetes with NAFLD. Further study on pathogenesis of type 2 diabetes with NAFLD should be performed.