Purpose: To review renal pathological changes in diabetes, which include thickening of all renal extracellular basement membranes and the mesangial matrix and, to a lesser extent, mesangial cell expansion. Critical renal lesions in diabetic nephropathy: Two renal lesions appear critical in diabetic nephropathy. Mesangial expansion out of proportion to the size of the glomerulus is inversely related to proteinuria, hypertension and a declining glomerular filtration rate. Arteriolar hyalinosis is related to global glomerulosclerosis and both are correlated with the clinical features of nephropathy. By the time renal dysfunction is clinically detectable, these lesions tend to be advanced. Interstitial volume may be increased in insulin-dependent diabetes mellitus, particularly in areas containing sclerotic glomeruli or marked tubular atrophy. Future research: Longitudinal studies of renal structure and function and a simultaneous study of potential risk factors and pathways of injury are necessary to develop more refined predictors and clearer pathogenic concepts of this important diabetic complication.