Objective  To establish the mouse model of nonalcoholic steatohepatitis induced by high fructose diet, high fat diet, and compound high fructose diet and explore the best diet structure. Methods  A total of 60 C57BL/6J mice were randomly divided into the high fructose group, high fat group, compound group, and control group. Differences of basic data, liver function, lipid metabolism, TNF-α, IL-6, and pathological changes of groups were compared after the model was established for 4, 8, and 12 weeks. Results  Compared with the control group, the body weight, wet liver weight, and Lee’s index of other groups were significantly higher (P<0.01). The increase of body weight of the compound group was more significant than that of the high fat group and high fructose group after 12 weeks (P<0.05). H-E staining indicated that except the control group, mice of other three groups had different degrees of macrosteatosis and significant intralobular inflammatory cell infiltration was only observed in mice of the compound group. Results of serum test showed that after 12 weeks, TG and CHO levels of the compound group and high fat group significantly increased and increases of ALT, AST, TNF-α, and IL-6 of the compound group were more significant than those of the high fat group and high fructose group. Conclusion  High fat and fructose diet for 12 weeks can successfully establish the mouse model for studying the nonalcoholic steatohepatitis.