Aim To study the ameliorative effect of sesamin(Ses) on endothelial dysfunction in diabetic rats and related mechanism.Methods Diabetic rats were induced by low dose streptozotocin(STZ) and fed with high-fat diet.Then,rats were randomly divided into model group and Ses(120,60 mg·kg-1·d-1,respectively ig,for 8 weeks.) groups.In addition,control group was set up.Eight weeks later,rats were sacrificed,the malondialdehyde(MDA) content,total antioxidative capacity(T-AOC) in serum were tested,and the protein expression of endothelial nitric oxide synthase(eNOS),nitrotyrosine(NT) and nicotinamide adenine dinucleotide phosphate(NADPH) oxidase subunit P47phox in aortas were deteced by Western blotting.In addition,vasorelaxation response to acetylcholine(ACh),and functional assessment of nitric oxide(NO) bioactivity were also determined in aortic rings.Results Compared with model group,vasodilation response of Ses(120 mg·kg-1) group was significantly improved.The MDA content was markedly decreased,T-AOC and NO level were increased.The protein expression of eNOS was significantly increased,while NT and P47phox were significantly decreased.Conclusion Ses can improve endothelial dysfunction through alleviated oxidative stress,enhance NO bioavailability by up-regulating eNOS expression and down-regulating NT and P47phox expression.