A host of diabetes-related changes in the central nervous system (CNS) has been recognized. The underlying causes of these changes are multiple. An important contributor to the changes in the CNS is the blood-brain barrier (BBB). Diabetes is associated with changes in both the barrier and transport functions of the cerebral microvessels. Structural changes in cerebral microvessels may account for some of the observed changes. Additional mechanisms include alterations in hemodynamic variables such as arteriovenous shunting, changes in biophysical properties and biochemical compositions of the endothelial cells including changes in lipid fluidity and composition, and alterations of neurotransmitter activity in the cerebral microvessels, notably altered beta adrenergic neurotransmission. These observations indicate that the CNS is not immune against the microangiopathic complications commonly found in various tissues of diabetic animals.