Hyperglycemia causes vascular complications of diabetes possible by the activation of protein kinase C (PKC). We have provided substantial evidence that activation of PKC can lead to a whole host of vascular dysfunction in diabetes. The activation of PKC induced by hyperglycemia appears to be due to an increase in diacylglycerol (DAG) levels, a physiological activator of PKC. Studies involving cultural cells, animal models of diabetes and patients have shown that inhibition of PKC by specific PKC inhibitor was able to reverse many of the vascular dysfunctions in the retina, kidney and cardiovascular systems induced by either hyperglycemia or diabetes. In addition high doses of vitamin E were shown to decrease the level of DAG and PKC induced by diabetes or hyperglycemia. Thus animal and clinical studies have shown that high doses of vitamin E treatment can apparently reverse some of the changes in the retinal and renal vessels.