Abstract: Objective To observe the expression of suppressors of cytokine signaling 3(SOCS-3),insulin receptor substrate-1(IRS-1)and phospho-IRS-1(PIRS-1^Ser307)in liver and skeletal muscle,and to explore molecular mechanisms of insulin resistance in diabetes rats models. Methods Forty male SD rats were randomly divided into two groups,the control group(20 male rats)fed with standard diet,and the Diabetes group(20 male rats)were fed with high sucrose-fat diet for 4 weeks and then injected intraperitoneally with streptozotocin(STZ),16 male rats met the criteria of type-2 diabetes.The expressions of SOCS-3,IRS-1 and PIRS-1^Ser307 in liver and skeletal muscle were detected by Real-time PCR and Western blot.The data were analyzed by T-test and Pearson linear correlation analysis. Results ①AS compared with control group,diabetes group showed that mRNA and protein expression of IRS-1 of liver and skeletal muscle were decreased(P<0.05),the expression of SOCS-3 and PIRS-1^Ser307 were increased(P<0.05).②The expression of SOCS-3 in liver and skeletal muscle were negatively correlated with IRS-1(r=-0.865,-0.756,P<0.05) and positively with PIRS-1^Ser307 in diabetes group(r=0.678,0.663,P<0.05). Conclusion Diabetes rats possibly produced insulin resistance by up-regulating SOCS-3 expression,by decreasing IRS-1 and increasing its serine phosphorylation levels in liver and skeletal muscle.