Aim:To examine the effects ofAstragalus polysaccharide (APS),a component ofan aqueous extract of Astragalus membranaceus roots,on protein tyrosine phos-phatase 1B (PTP1B),a negative regulator of insulin-receptor (IR) signaltransduction,and its potential role in the amelioration of insulin resistance.Methods:Ten-week-old fat-fed streptozotocin (STZ)-treated rats,an animal modelof type Ⅱ diabetes mellitus (TIIDM),were treated with APS (400 mg/kg po) for 5weeks.Insulin sensitivity was identified by the insulin-tolerance test.Further analy-ses on the possible changes in insulin signaling occurring in skeletal muscle andliver were performed by immunoprecipitation or Western blotting.PTP1B activ-ity was measured by an assay kit.Results:The diabetic rats responded to APSwith a significant decrease in body weight,plasma glucose,and improved insulinsensitivity.The activity and expression of PTP1B were elevated in the skeletalmuscle and liver of TIIDM rats.Thus the insulin signaling in target tissues wasdiminished.APS reduced both PTP1B protein level and activity in the muscle,but not in the iiver of TIIDM rats.Insulin-induced tyrosine phosphorylation of theIR β-subunit and insulin receptor substrate-1 (IRS-1) were increased in the muscle,but not in the liver of APS-treated TIIDM rats.There was no change in the activityor expression of PTP1B in APS-treated normal rats,and blood insulin levels didnot change in TIIDM rats after treatment with APS.Conclusion:APS enablesinsulin-sensitizing and hypoglycemic activity at least in part by decreasing theelevated expression and activity of PTP1B in the skeletal muscles of TIIDM rats. Aim: To examine the effects of Astragalus polysaccharide (APS), a component ofan aqueous extract of Astragalus membranaceus roots, on protein tyrosine phos-phatase 1B (PTP1B), a negative regulator of insulin-receptor (IR) signaltransduction, and its potential role in The amelioration of insulin resistance.Methods:Ten-week-old fat-fed streptozotocin (STZ)-treated rats,an animal model of type II diabetes mellitus (TIIDM),were treated with APS (400 mg/kg po) for 5weeks.Insulin Sensitivity was identified by the insulin-tolerance test.Further analy-ses on the possible changes in insulin signaling occurring in skeletal muscle and liver were performed by immunoprecipitation or Western blotting.PTP1B activity was measured by an assay kit.Results:The diabetes rats Responded to APSwith a significant decrease in body weight,plasmg glucose,and improved insulinsensitivity.The activity and expression of PTP1B were elevated in the skeletalmuscle and liver of TIIDM rats.Thus the insulin signaling in target Tissues wasdiminished.APS reduced both PTP1B protein levels and activity in the muscle, but not in the iiver of TIIDM rats.Insulin-induced tyrosine phosphorylation of theIR β-subunit and insulin receptor substrate-1 (IRS-1) were increased in the muscle ,but not in the liver of APS-treated TIIDM rats.There was no change in the activityor expression of PTP1B in APS-treated normal rats,and blood insulin levels did not change in TIIDM rats after treatment with APS.Conclusion:APS enablesinsulin-sensitizing And hypoglycemic activity at least in part by decreasing theelevated expression and activity of PTP1B in the skeletal muscles of TIIDM rats.