Although the evolution of diabetic nephropathy is brought about mostly by persistent hyperglycemia, its progression may be influenced by various other factors such as hypertension and dietary protein intake. It has been recently suggested in the literature that the gene polymorphism of angiotensin converting enzyme (ACE) might be associated with the development of diabetic nephropathy, because the DD genotype of ACE gene is closely associated with the presence of nephropathy in diabetic subjects. However, in our present analysis the frequency of the DD genotype in patients with non-insulin dependent diabetes is not significantly related to the presence or absence of nephropathy. It remains to be clarified by multi-center analysis using large numbers of patients whether the gene polymorphism of ACE is related to the progression of diabetic nephropathy to renal failure. Furthermore, it has been postulated that the interstitial fibrosis evaluated in renal biopsy specimens is significantly correlated with the declining of renal function in diabetic patients. However, it is not possible to clinically quantitate the interstitial fibrosis without performing renal biopsy. We have recently found that the urinary excretion of type IV collagen is significantly increased in diabetic patients. Moreover, the increase in urinary type IV collagen is well correlated with the amount of urinary albumin. Since type IV collagen in the urine is probably derived from tubulointerstitial tissue, it is likely that the increased amount of type IV collagen in the urine may reflect the fibrotic change in diabetic kidneys. Whether the increase in urinary type IV collagen is able to predict for the progression of diabetic nephropathy in the future should be examined.