Diabetes is characterized by hyperglycemia, a relative lack of insulin, and an inclination to vascular disease and neuropathy. The link between diabetes and vascular disease is not understood, but autonomic dysfunction could partly account for alterations in reactivity of diabetic blood vessels to neurotransmitters and circulating hormones. Changes in local control of vascular tone, such as imbalance in production of relaxing and contracting factors by the endothelium, may be related to the initiation and maintenance of abnormal vascular reactivity characteristically seen in diabetic vascular complications. The emphasis is to discuss functional changes of blood vessel adrenergic neuroeffector mechanisms and endothelial cell dysfunction, together with the complex interrelationship of cyclooxygenase catalysis, protein kinase C activity, sodium-potassium ATPase activity, and flux through the polyol pathway. This review focuses on the common mechanisms by which hyperglycemia causes changes in vascular function.