OBJECTIVE Prolonged exposure to hyperglycemia is one of the key factors to induce progressive diabetic nephropathy in humans. We examined whether or not the same phenomenon is observed in a nonobese type 2 diabetes model, in Goto-Kakizaki (GK) rats. METHODS Urine and serum samples from GK and Wistar rats were collected to measure biochemical parameters of the renal function. The kidneys of these animals were histopathologically and immunohistochemically analyzed. RESULTS Moderate hyperglycemia was sustained in GK rats during the experimental period. Noticeable morphological changes in the kidneys such as segmental glomerulosclerosis and tubulointerstitial fibrosis were observed only at 24 months of age. The expression of alpha smooth muscle actin and type IV collagen in glomeruli and tubulointerstitium was increased at 12 months of age and later. The macrophage infiltration was increased in parallel with the progression of renal lesions. The excretion of urinary protein in GK rats was increased only at 24 months of age. Moreover, the functional and morphological changes in Wistar rats were less severe than in age-matched GK rats. CONCLUSIONS We conclude that renal changes of GK rats at a late stage were similar to those of progressive human diabetic nephropathy and that prolonged hyperglycemia may play a more crucial role in inducing progressive diabetic nephropathy than aging and obesity.