AimThe aim of this study was to investigate whether ezetimibe has a protective effect on β-cell function in diabetic state.Methods8-week-old db/db mice were randomized to ezetimibe 10 mg/(kg·d), or placebo.The age-matched nondiabetic littermates db/m mice were treated with placebo as the controls.After 6 weeks’ treatment, intraperitoneal glucose tolerance test and immunohistochemical staining for insulin were performed.Islet perifusion were performed to evaluate kinetics of insulin release by using islet perfusion system.ResultsFasting blood glucose (FBG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC) were lower in ezetimibe group than that in db/db group after 6 weeks’ treatment.Ezetimibe provided an improvement of glucose tolerance and greatly rescued islet β-cell mass.Ezetimibe treatment also improved first-phase insulin response.ConclusionEzetimibe treatment effectively improved glucose tolerance and β-cell function by significantly restored first-phase insulin secretion on db/db mice.