The kidneys as a target organ for secondary microvascular complications of diabetes mellitus represents a health problem of enormous social cost. Recent studies in man and animals strongly support the concept that the primary responsibility for diabetic nephropathy rests with the metabolic derangements of the diabetic state. However, these metabolic derangements have complex biological effects; it is unlikely that hyperglycemia, per se, produces all of the nephropathic influences of diabetes. Alterations in microvascular hemodynamics in diabetes probably contribute to glomerular pathology. These alterations may be based upon disturbed vasoactive control mechanisms regulating angiotensin and prostaglandin secretion and metabolism. Although much remains to be learned about the pathogenesis of glomerular basement membrane and mesangial thickening in diabetes, these central structural abnormalities appear separable. Mesangial thickening is reversible by cure of the diabetic state in rats whereas glomerular basement membrane thickening is not. Treatment for the diabetic patient with end-stage renal failure has recently improved markedly. Although presently, kidney transplants from living related donors appear best, cadaver transplants and long-term hemodialysis are reasonable options.