Abstract: Objective To study the effect of different doses of liraglutide on insulin resistance（IR） in model rats with nonalcoholic fatty liver disease（NAFLD）. Methods High fat diet was given to 50 male Sprague-Dawley rats to establish NAFLD and 32 rats with successful NAFLD were randomly divided into 4 groups,e.g. group A （model group,n=8）,and liraglutide were given in group B [0.9 mg·kg-1·d-1,n=8],group C [1.8 mg·kg-1·d-1,n=8] and group D[3.6 mg·kg-1·d-1,n=8]. Rats were sacrificed after 4 weeks of medicine intervention. Data of body weight and liver weight were recorded. Blood from the abdominal aorta and livers were collected. Liver index,blood glucose,insuli （FINS）,blood lipids（TG,TC）,transaminase（ALT,AST）,malondialdehyde （MDA）,and glutathione peroxidase （GSH-Px）,superoxide dismutase （SOD） and tumor necrosis factor alpha （TNF-alpha） in liver tissues were detected. Results Compared with in the model group,the rat body weight,liver index,ALT,FINS,FPG,HOMA-IR,MDA in blood and TG,TC,MDA in liver tissues decreased significantly in intervention groups （P<0.05）,and in group D with highest dose of liraglutide gained the most decrease in the above index than in the other two intervention groups（P<0.05）;Compared with in model group, the GSH-Px and SOD in intervention groups significantly increased（P<0.05）,and GSH-Px and SOD in group D increased the most（P<0.05）;There was no significant difference of TNF-α among all the groups. Conclusion Liraglutide can significantly reduce the liver index, serum lipid and blood glucose in rats with NAFLD,and improve IR,and the treatment effect is dose-dependent.

Key words: Nonalcoholic fatty liver disease, Liraglutide, Insulin resistance, Glutathione peroxidase, Superoxide dismutase, Rats