Abstract: Objective To study the effect of emodin(EM) on insulin sensitivity in hepatic tissue of mice with KKAy diabetes mellitus(DM) and its mechanism of decreasing blood glucose. Methods Twenty specific pathogen free(SPF) KKAy mice were randomly divided into model group(DM group) and EM treatment group according to their plasma glucose level.Ten normal C57BL/6J mice served as a normal control(NC) group.The mice received intragastric lavage with EM for 8 weeks.Then,their fasting serum glucose(FPG) and insulin levels were measured,insulin sensitivity index(ISI),total triacylglycerol(TG),and total cholesterol(TC) were detected,and expression levels of PPAR-γ and GluT-2mRNA in their hepatic tissue were measured by immunohistochemistry or RT-PCR. Results The FPG,TG and TC levels were higher while the ISI and expression levels of PPAR-γ and GluT-2mRNA were lower in DM group than in NC group(P<0.05).The FPG,TG and TC levels were significantly lower while the ISI and expression levels of PPAR-γ were significantly higher in EM treatment group than in DM group(P<0.05).A significant difference was found in the integrated optical density(IOD) between EM treatment group and DM group(P<0.05). Conclusion EM can up-regulate the expression levels of PPAR-γ and GluT-2mRNA,and down-regulate the insulin sensitivity in mice with KKAy DM.