Objective:To observe changes of glucose tolerance and insulin function of CETP transgenic mice with ovariectomy and estrogen replacement. Methods:Fifteen female CETP transgenic mice were randomly divided into three groups,including the sham group,the ovariectomy group and the estrogen replacement therapy group. The ovariectomy group and the estrogen replacement therapy group were underwent ovariectomy. Two weeks after operation,the estrogen replacement therapy group was given estrogen,while the sham group and the ovariectomy group were given equal dosages of olive oil. Fasting glucose was measured four weeks after operation. Islets were extracted to test islet function by intraperitoneal glucose tolerance test(IPGTT)and GSIS eight weeks after operation. Results:Mice of the ovariectomy group showed significantly increased fasting glucose levels 8 weeks after operation compared with those of the sham group(P < 0.05). The blood glucose of mice at all time points of IPGTT increased significantly than those in the sham group(P < 0.05). GSIS showed that insulin secretion had a decreased tendency. While after ovariectomy,estrogen replacement therapy significantly improved the above changes. Blood glucose levels at 0,15 and 30 min of IPGTT were decreased significantly(P < 0.05). Insulin secretion function of GSIS also had an improved tendency. Conclusion:After ovariectomy,CETP transgenic mice have impaired islet function and glucose tolerance,which lead to the increase of fasting blood glucose and the decrease of glucose stimulated insulin secretion levels. Estrogen replacement plays a protective role in the harmful effects of ovariectomy on pancreatic is let βcells.