Abstract: AIM:To investigate the protective effect of melatonin on functions of vascular endothelium in patients with type 2 diabetes mellitus (T2DM). METHODS: Sixty patients with T2DM without significant vascular complications were randomly divided into treatment group and control group and 28 healthy individuals were included as normal controls in the study. Patients in the control group were given conventional therapy including diabetic diet, regular aerobic exercise and insulin. On the basis of the conventional therapy, patients in the treatment group were given melatonin (MLT) (6 mg/day) at 21:00 h. All patients were treated for 6 months. Blood pressure, fasting plasma glucose (FPG), 2 h postprandial blood glucose (2hPPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), lowdensity lipoprotein cholesterol (LDLC) and highdensity lipoprotein cholesterol (HDLC) were measured before and after the therapy. Body mass index (BMI) was also calculated. Endotheliumdependent flowmediated vasodilation (FMD) and endotheliumindependent nitroglycerinmediated vasodilation (NMD) of brachial arterial blood were measured with highresolution extravascular ultrasound technique before and after the therapy. RESULTS: FPG, 2hPPG, HbA1c, TG, and LDLC were higher (P<001) and HDLC in diabetic groups were lower (P<005) than those in normal control group before treatment. After the 6month treatment, TG and LDLC decreased, BMI and LDLC increased but without significant difference in the above statistics. FBG, 2hPPG and HbA1c showed no change. Before treatment, no significant difference in the baseline vessel size and NMD was found between diabetic groups and normal control group but FMD decreased significantly (P<001). After the 6month treatment, no significant changes were found in baseline vessel size and NMD in diabetic groups compared with those before treatment. FMD in patients of the treatment group and control group increased significantly after treatment (P<005 or P<001). FMD in patients of the treatment group was significantly higher than in the control group (P<005). CONCLUSION: FMD is impaired in patients with T2DM without significant vascular complications. MLT can markedly improve vascular endothelial functions in patients with T2DM.