Endothelial dysfunction plays a crucial role in the development of diabetic vascular disease. The endothelium controls vascular tone by producing vasodilator mediators, such as nitric oxide (NO), prostacyclin, and an endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium-dependent vasodilation has been observed in various vascular beds of diabetic animal models and humans with type 1 and type 2 diabetes. Several mechanisms contribute to this dysfunction, including impaired signal transduction, substrate availability, release of EDHF, increased destruction of EDHF, enhanced release of endothelium-derived constricting factors, and decreased sensitivity of vascular smooth muscle to EDHF. Hyperglycemia-induced endothelial dysfunction may be mediated by activation of protein kinase C, increased polyol pathway activity, non-enzymatic glycation, and oxidative stress. Correcting these pathways, along with the administration of ACE inhibitors and folate, has been shown to improve endothelium-dependent vasodilation in diabetes. The mechanisms of endothelial dysfunction vary depending on the diabetic model and vascular bed studied, emphasizing the need for clinically relevant models in future research.Endothelial dysfunction plays a crucial role in the development of diabetic vascular disease. The endothelium controls vascular tone by producing vasodilator mediators, such as nitric oxide (NO), prostacyclin, and an endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium-dependent vasodilation has been observed in various vascular beds of diabetic animal models and humans with type 1 and type 2 diabetes. Several mechanisms contribute to this dysfunction, including impaired signal transduction, substrate availability, release of EDHF, increased destruction of EDHF, enhanced release of endothelium-derived constricting factors, and decreased sensitivity of vascular smooth muscle to EDHF. Hyperglycemia-induced endothelial dysfunction may be mediated by activation of protein kinase C, increased polyol pathway activity, non-enzymatic glycation, and oxidative stress. Correcting these pathways, along with the administration of ACE inhibitors and folate, has been shown to improve endothelium-dependent vasodilation in diabetes. The mechanisms of endothelial dysfunction vary depending on the diabetic model and vascular bed studied, emphasizing the need for clinically relevant models in future research.