Objective To investigate Schistosoma japonicum infection on mice high-fat diet of insulin resistance. Methods 36 male C57 BL/6 J mice were randomly assigned into three equal groups: normal control group ( NC group) , high-fat diet group ( HF group) and high-fat diet with Schistosoma japonicum infected group ( HSJ group) . Specimen was collected 6 and 12 weeks after high-fat diet, separately. The levels of fasting blood glucose ( FBG) , fasting plasma insulin resistance index ( FINS) and insulin ( HOMA-IR) were detected. Interferon-γ( IFN-γ) ,in-terleukin-4 ( IL-4 ) and singal transductor and activator of transcription-4 ( STAT4 ) singal transductor and activator of transcription-6 (STAT6)were detected by ELISA and immunohistochemical method. Results The mice from HF group showed higher levels of HOMA-IR than those from NC groups by the end of 6 and 12 weeks after infection( P<0. 01 );the levels of HOMA-IR in mice from HSJ group were lower than NC group and HF group by the end of 12 weeks(P<0. 05);the levels of IL-4 in mice from HSJ group were higher than NC group and HSJ group by the end of 6 and 12 weeks after infection ( P<0. 05 ); the levels of STAT6 in mice from HSJ group were higher than HF group by the end of 12 weeks after infection ( P<0. 05 );the levels of STAT4 in mice from HF group were higher than NC group by the end of 6 and 12 weeks after infection. Conclusion Schistosome japonicum chronic infection may improve insulin resistance in obese mice with induced STAT6 protein expressed in liver tissue and secrete IL-4,providing new ideas for the prevention and treatment of diabetes.