It was studied whether fenofibrate alone or combinational treatments of fenofibrate and 17β-estradiol regulates serum lipid levels, and whether the effects of fenofibrate on serum lipid metabolism are affected by co-administration of 17β-estradiol in low-fat diet-fed ovariectomized female mice. Compared with low-fat diet-fed controls, mice treated with fenofibrate alone and mice treated with fenofibrate and 17β-estradiol didn’t decrease body weight at 8 weeks. Fenofibrate alone or combinational treatments of fenofibrate and 17β-estradiol did not regulate serum levels of total cholesterol and HDL-cholesterol. Fenofibrate decreased plasma levels of LDL-cholesterol and triglycerides compared with controls. The combinational treatments of fenofibrate and 17β-estradiol showed more beneficial effects on triglycerides than fenofibrate alone. Therefore, the present study found that serum triglycerides reduced by fenofibtae treatment alone could be more improved by combinational treatments of fenofibrate and 17β-estradiol in low-fat diet-fed ovariectomized female mice.