〔Abstract〕 Objective To investigate the effects of liraglutide on ERp46 protein, adiponectin and oxidative stress in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD), and to explore the possible mechanism of liraglutide in improving fatty liver. Methods Thirty two male rats were randomly divided into high-fat diet group(HFD,n=20) and normal diet group(ND,n=12). After NAFLD models were successfully established by high-fat diet for 12 weeks, HFD were randomly divided into liraglutide group and placebo group, and hypodermic injection of liraglutide 0.6 mg/(kg·d) and isopyknic saline respectively. Rats were all killed at the end of 28 weeks. The levels of weight, liver mass, biochemical index and inflammatory factors were measured, and liver tissues were stained with hematoxylin-eosin. Real-time PCR and Western blot were used to detect the expression of ERp46 mRNA and protein in liver tissue. Results Compared with placebo group, the expression levels of ERp46 and adiponectin in liver tissue of liraglutide group were increased, and the body weight, liver index, alanine aminotransferase, fasting insulin, insulin resistance index, cholesterol, triglyceride, low densith lipoprotein, and the liver levels of triglyceride, cholesterol, free fatty acids, tumor necrosis factor α and malonaldehyde decreased,the hepatic homogenate superoxide dismutase(SOD) increased and the degree of hepatic steatosis decreased(P<0.05). Conclusion The mechanism of liraglutide in improving non-alcoholic fatty liver may be related to the up-regulation of ERp46 protein expression and adiponectin level in liver tissue, and inhibition of endoplasmic reticulum stress and alleviation of oxidative stress in liver tissue.