Aim To investigate the effect of long-term folate supplementation on endothelial function of thoracic aortea in rats with type 2 diabetes mellitus and explore its mechanisms.Methods After the rat model of type 2 diabetes mellitus was established by a single injection of low dose streptozotocin(STZ)after 6 weeks of high calorie diet,the animals were divided into model group,low-dose folate group and high-dose folate group.Other 11 rats were employed as normal control group.The levels of nitric oxide(NO),superoxide dismutase(SOD)and maleic dialdehyde(MDA)in the serum were determined.Acetylcholine-induced endothelium-dependent vascular relaxation(EDVR)of aorta rings was tested.Results The levels of NO and SOD in serum were significantly lower and the level of MDA in serum was notably higher in model group than those in normal control group;After 11 weeks of folate supplementation,compared with model group,the levels of NO and SOD in serum significantly increased in low-dose folate group and high-dose folate group,while the level of MDA in serum decreased markedly.Compared with normal control group,EDVR responses to acetylcholine(Ach)of each concentration were obviously weakened in model group.Compared with model group,EDVR responses to Ach of each concentration were significantly improved in low-dose folate group and high-dose folate group,and further increment of folate led to no further improvement of EDVR response.Conclusion Long-term folate supplementation can effectively prevent the EDVR impairment.The effect may be associated with the increase of NO formation and its antioxidant effect.