Abstract: Objective: To establish the nonalcoholic fatty liver disease(NAFLD) model in C57BL/6 mice using D12492 high-fat feed,and provide the basis in studying the NAFLD.Methods: Forty healthy male C57BL/6 mice were randomly divided into the control group and model group(20 mice each group).The control group and model group were fed with the normal feed and high-fat feed,respectively.After 4,8,12 and 16 weeks of feed,the body weight,liver weight and liver tissue homogenate were observed,the serum levels of ALT,total cholesterol,low-density lipoprotein and liver triglyceride were detected,and the liver pathology examination was implemented.Results: The body weight after 4 weeks of feed and liver weight after 8 weeks of feed in model group were higher than those in control group,respectively(P<0.05 to P<0.01).Compared with the control group,the serum ALT level in model group after 8 weeks of feed increased(P<0.05 to P<0.01).The levels of serum total cholesterol and low-density lipoprotein in model group at each time-point were higher than those in control group(P<0.05 to P<0.01).Compared with the control group,the content of triglyceride in model group after 12 weeks of feed increased(P<0.05 and P<0.01).The liver tissue staining showed that the liver tissue steatosis,liver cells swelling,fat cavitation in cytoplasm and liver cells inflammatory change were identified in model group after 12-week of feed,and the liver cells inflammatory change aggravated and a large number of inflammatory cells infiltrated in model group after 16-week of feed.Conclusions: The NAFLD model induced by high fat-diet is an ideal animal model,which is easy to establish and repeatable,and can provide stable animal model for the study of mechanism and clinical treatment of NAFLD.