Objective To investigate the influence of synergistic effect of estradiol and testosterone on the level of lipids and coagulation function in mice with hyperlipidemia. Methods We established a maouse model in hyperlipidmia, giving estradiol(1 μg/d), testosterone(7 μg/d) or estradiol combined testosterone(1 μg/d E2+7Tμg/d), respectively. After 14 weeks, we collected the blood from the mice, separated the serum to detect the lipids level, separated the plasma to test the coagulation function. Result Compared with controls, after high-fat diet, the serum level of total cholesterol(TC), triglyceride(TG), high density lipoprotein(HDL) were significantly increased, PT and APTT were shorter(P<0.05). However, after treating with estradiol combined testosterone, compared with cases, the serum level of C,TG and HDL were lower and PT, APTT were longer(P<0.05), had no significance with controls. Conclusion The synergistic effect of estradiol and testosterone can mediate the lipids, reduce the level of LDL, regulate the coagulation function, reduce the risk of coronary heart disease, and also provide a new strategy for hormone therapy in coronary heart disease.