Aim To investigate the inhibiting effect of 17-β estradiol on insulin resistance induced by the high fructose diet in ovariectomized rats. Methods Thirty six ovariectomized female Sprague-Dawley(S-D)rats were fed with the high fructose diet for eight weeks to induce insulin resistance. Then they were randomly divided into three groups: the model group, the 17-β estradiol replacement group,the vehicle control group.The normal control group twelve rats were fed with the normal diet for eight weeks.Body weight(BW),systolic blood pressure(SBP),glucose tolerance,plasma triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDLC)and low density lipoprotein cholesterol(LDLC),fasting blood sugar(FBS)and fasting serum insulin(FSI)and insulin sensitivity index(ISI)were measured. Results Compared with the normal control group,BW(p<0.05),SBP(p<0.05), the levels of plasma TG,TC,LDLC,FBS(all p<0.05) and FSI(p<0.01) were increased significantly and the plasma HDLC level was decreased significantly (p<0.05) in the model group. Glucose tolerance was decreased significantly(p<0.05)and injury of pancreatic β-cell was observed in the model group.ISI was decreased significantly(p<0.05) and insulin resistance was arisesed in the model group.Compared with the model group,these effects were reversed, ISI was increased significantly(p<0.05) and insulin resistance was inhibited in the 17-β estradiol replacement group. Conclusion 17-β estradiol inhibited insulin resistance,injury of pancreatic β-cell and lipid dysbolism induced by the high fructose diet in ovariectomized rats.These findings suggested that estradiol in female rat might provide protection againt the effect of the high fructose diet,which caused hypertension,insulin resistance,injury of pancreatic β-cell and lipid dysbolism.