Endothelial dysfunction is a key factor in the development of diabetic vascular disease. The endothelium regulates vascular smooth muscle tone through the production of vasodilator mediators, including nitric oxide (NO), prostacyclin, and an elusive endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium-dependent vasodilation has been observed in various vascular beds in animal models and in humans with type 1 and 2 diabetes. Several mechanisms contribute to endothelial dysfunction, including impaired signal transduction, reduced EDRF production, increased EDRF destruction, and enhanced release of endothelium-derived constricting factors. Key mediators of hyperglycaemia-induced endothelial dysfunction include protein kinase C activation, increased polyol pathway activity, non-enzymatic glycation, and oxidative stress. Correcting these pathways, along with ACE inhibitor and folate administration, has shown improvement in endothelium-dependent vasodilation in diabetes. The mechanisms of endothelial dysfunction vary depending on the diabetic model and vascular bed, emphasizing the need for clinically relevant models in future research. Endothelial dysfunction in diabetes is associated with impaired endothelium-dependent vasodilation, which is influenced by factors such as hyperglycaemia, oxidative stress, and altered metabolic pathways. Aldose reductase activity, protein kinase C activation, and advanced glycation end products (AGEs) are key contributors to endothelial dysfunction. Oxidative stress, resulting from increased reactive oxygen species, plays a significant role in endothelial dysfunction by inactivating NO and impairing vascular smooth muscle function. Antioxidants such as superoxide dismutase, catalase, and vitamin E have shown potential in improving endothelial function in diabetes. Therapeutic strategies targeting endothelial dysfunction include ACE inhibitors and folate, which have demonstrated benefits in improving endothelial function in diabetic patients. However, the effectiveness of these treatments may vary depending on the vascular bed and the underlying mechanisms of dysfunction. Future research should focus on understanding the complex pathophysiology of endothelial dysfunction in diabetes and developing targeted therapies to improve vascular outcomes. The importance of selecting clinically relevant models for studying endothelial dysfunction cannot be overstated, as the mechanisms of dysfunction may differ between vascular beds and diabetic models. Overall, endothelial dysfunction is a critical target for therapeutic intervention in diabetic vascular disease.Endothelial dysfunction is a key factor in the development of diabetic vascular disease. The endothelium regulates vascular smooth muscle tone through the production of vasodilator mediators, including nitric oxide (NO), prostacyclin, and an elusive endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium-dependent vasodilation has been observed in various vascular beds in animal models and in humans with type 1 and 2 diabetes. Several mechanisms contribute to endothelial dysfunction, including impaired signal transduction, reduced EDRF production, increased EDRF destruction, and enhanced release of endothelium-derived constricting factors. Key mediators of hyperglycaemia-induced endothelial dysfunction include protein kinase C activation, increased polyol pathway activity, non-enzymatic glycation, and oxidative stress. Correcting these pathways, along with ACE inhibitor and folate administration, has shown improvement in endothelium-dependent vasodilation in diabetes. The mechanisms of endothelial dysfunction vary depending on the diabetic model and vascular bed, emphasizing the need for clinically relevant models in future research. Endothelial dysfunction in diabetes is associated with impaired endothelium-dependent vasodilation, which is influenced by factors such as hyperglycaemia, oxidative stress, and altered metabolic pathways. Aldose reductase activity, protein kinase C activation, and advanced glycation end products (AGEs) are key contributors to endothelial dysfunction. Oxidative stress, resulting from increased reactive oxygen species, plays a significant role in endothelial dysfunction by inactivating NO and impairing vascular smooth muscle function. Antioxidants such as superoxide dismutase, catalase, and vitamin E have shown potential in improving endothelial function in diabetes. Therapeutic strategies targeting endothelial dysfunction include ACE inhibitors and folate, which have demonstrated benefits in improving endothelial function in diabetic patients. However, the effectiveness of these treatments may vary depending on the vascular bed and the underlying mechanisms of dysfunction. Future research should focus on understanding the complex pathophysiology of endothelial dysfunction in diabetes and developing targeted therapies to improve vascular outcomes. The importance of selecting clinically relevant models for studying endothelial dysfunction cannot be overstated, as the mechanisms of dysfunction may differ between vascular beds and diabetic models. Overall, endothelial dysfunction is a critical target for therapeutic intervention in diabetic vascular disease.