Objective To investigate the protective effect of rhein lysinate (RHL)on the liver of the models with diabetic rats,and to provide basis for research on treatment of fatty liver in the patients with diabetes mellitus. Methods The models of diabetic rats were established by intraperitoneally injecting streptozotocin(STZ).40 rats were divided into control,model,25 mg·kg-1 RHL,and 50 mg·kg-1 RHL groups(n=10).The levels of malonaldehyde (MDA)and the activities of superoxide dismutase (SOD)and glutathione peroxidase (GSH-Px) were detected by thiobarbituric acid method, pyrogallol autoxidation method, and NADPH coupling method, respectively.The pathological changes of liver tissue were observed by hematoxylin and eosin (HE)staining;the content of fat in liver tissue was observed by Nile red staining;the expression levels of fat synthesis-related proteins were detected by Western blotting method.Results Compared with control group,the body weight of the rats in model group was decreased and the levels of blood glucose,total cholesterol(TC)and triglyceride(TG)were increased (P<0.05);the activities of SOD and GSH-Px in liver tissue were decreased (P<0.05);there were a plenty of fat vacuoles and fat accumulation in liver tissue. The signal pathway of fat synthesis-related ERK1/2-SREBP-1c was activated in model group;compared with model group,it was inhibited in 25 and 50 mg· kg-1 RHL groups (P<0.05).Compared with model group,the blood glucose,TC and TG of the rats in 25 and 50 mg ·kg-1 RHL groups were decreased (P<0.05);the activities of SOD and GSH-Px were increased (P<0.05);however the body weight had no change. Compared with model group, the fatty vacuoles and the fatty accumulation of liver tissue in 25 and 50 mg·kg-1 RHL groups were decreased. Conclusion The hepatic protection of RHL is correlated with the inhibition of oxidative stress, fat degeneration and fatty accumulation of liver tissues.