Aims and Methods: This study was carried out to clarify whether the urinary excretion of type IV collagen (u-IV collagen) detected by specific radioimmunoassay, can be used as an indicator for the progression of diabetic nephropathy. Results: u-IV collagen was higher in diabetic subjects with microalbuminuria and overt proteinuria than those with normoalbuminuria, IgA nephropathy, membranoproliferative glomerulonephritis, membranous nephropathy, or control normal subjects. u-IV collagen was positively correlated with serum and urinary β2-microglobulin and negatively with creatinine clearance only in diabetic patients, but not in patients with other glomerular diseases. The serum type IV collagen was not different between all the groups, and not correlated with its urinary excretion. In the advanced diabetic nephropathy, immunoreactive type IV collagen was detected in glomerular basement membrane (GBM), tubular basement membrane and Bowman’s capsule much more than that in the normal kidney. Conclusion: These findings indicated increased production and degeneration of type IV collagen in diabetic nephropathy. It is suggested that augmented turnover of type IV collagen in GBM and tubular basement membrane results in increased concentrations of free u-IV collagen. Therefore, measurement of u-IV collagen may be a useful, specific indicator of the progression of diabetic nephropathy.