The clinical features and quantitative renal morphometry, including the index of mesangial expansion (IME), the index of arteriolar hyalinous change (IAHC), the percentage of globally sclerosed glomeruli (%GS), and interstitial volume fraction for total renal cortex (Vv int/T) of 67 Japanese non-insulin dependent diabetes mellitus (NIDDM) patients were examined. For the total subject population, Vv int/T correlated with urine protein, creatinine clearance, blood pressure, IME, IAHC and %GS, but not with duration of NIDDM. No significant difference in interstitial expansion between normo- and microalbuminuric patients was observed, and Vv int/T did not correlate with urine albumin excretion rate in those patients. However, in the area without hyalinized glomeruli and atrophic tubules, we found significant interstitial expansion and thickening of the tubular basement membrane (TBM) in patients without overt proteinuria as compared with those in the age-matched minimal change control group. This study confirmed that interstitial expansion in NIDDM progresses in parallel with glomerular and arteriolar lesions and that the expansion occurs concurrently with TBM thickening before the appearance of proteinuria.