Nephromegaly and mesangial matrix expansion observed in the diabetic kidney are all clues of a role of growth factors in the pathogenesis of these lesions. A growing body of evidence shows that changes in (1) insulin-like growth factor I regulation, and (2) the transforming growth factor beta loop exist in the kidney in the diabetic hypertrophic kidney and in diabetic glomerulosclerosis. However, other growth factors may be involved in some diabetic renal changes. The abnormalities in growth factor content and regulation, the role of growth factors in the diabetic kidney, and the effect of hyperglycemia and advanced glycosylation end products on growth factors in the kidney are reviewed.