Abstract: Objective To investigate the influence of chronic ethanol intake on insulin receptor(IR),insulin receptor substrate 21(IRS 21)mRNA exp ression in adipose tissue of rats and explore the possible molecular mechanism of the effect of alcohol on insulin sensitivity.Methods Fourty male Wistar rats were randomly divided into four groups on the basis of body weight:control group(C),low(L),moderate(M)and high alcohol group(H).The rats were adm in istrated with ethanol by gastric in tubation and the dose of each group was 0(control),0.8(L),1.6(M)and 2.4(H)g/kg·bw daily,respectively.Nineteen weeks later,serum was collected for testing of fasting plasm a glucose and insulin and HOM A-IR index of each group was calcu lated.Total adipose tissue RNA was extracted.The expression levels of IR,IRS-1 m RNA in adip ose tissue were detected by R T-PCR.Results Compared with the control group,the glucose concentration significantly increased in H ethanol group(P<0.05)and the insulin concentration significantly increased in L and Methanol groupd(P<0.05).HOMA-IR significantly increased in ethanol groups(P<0.05).IR,IRS21 mRNA exp ression remarkably increased in ethanol groups(P<0.05).Conclusion The study showed that chronic ethanol intake could induce insulin resistance.The increase of IR,IRS 21 mRNA exp ression in adiposetissue may be involved in the molecular mechanism of ethanol effects on insulin sensitivity.