Objective：To extract the flavonoids and polyphenol substances from mulberry leaves，observe its effect on reducing blood sugar and improving insulin resistance(IR)in type 2 diabetes mellitus(T2DM)model rats and study its molecular mechanism.Methods：Selected the male SD rats and divided them into the normal group，the model group，the metformin group and the mulberry leaves extract group.Established the T2DM model in addition to the normal group，gave the intervention of gastric perfusion for four weeks and observed the effect of drugs on general conditions，biochemical indexes and skeletal muscular pathology in model rats.Determined the mRNA and protein expression levels of insulin receptor substrates-1(IRS-1)，p85α of phosphoinositide 3-kinase(PI3K)and glucose transporter 4(GLUT4)in the skeletal muscle tissue.Results：Compared with the normal group，the levels of the fasting plasma glucose(FBG)，homeostasis model of assessment for insulin resistence index(HOMA-IR)，serum insulin，total cholesterol，triglyceride and low density lipoprotein in the model group were increased(P ＜ 0.05)；the mRNA and protein expressions in IRS-1，PI3K p85α and GLUT4 were obviously decreased(P ＜ 0.05).Compared with the model group， the levels of FBG， HOMA-IR， total cholesterol，triglyceride and low density lipoprotein in the mulberry leaves extract group were decreased(P＜ 0.05)；the mRNA and protein expressions in IRS-1，PI3K p85α and GLUT4 were obviously increased(P ＜ 0.05)；the FBG in the metformin group was decreased but the difference was no significant，there was no significant difference being found in the levels of serum insulin， HOMA-IR indexes， high density lipoprotein and triglyceride and the levels of total cholesterol and low density lipoprotein were decreased(P ＜ 0.05)；the mRNA and protein expressions in IRS-1，PI3K p85α and GLUT4 were increased but there was no significant difference.In addition，immunohistochemical analysis showed that when compared with the model group，the mulberry leaves extract group was presented as IRS-1 strong coloring.Conclusion：Mulberry leaves extract can reduce the body mass， blood glucose levels and the levels of total cholesterol， triglyceride and low density lipoprotein in T2DM rats to improve IR，and the effect of lowering blood sugar and blood lipid is completed through IRS-1/PI3K/GLUT4 signal pathway.