The microvascular complications of diabetes mellitus may be caused, in part, by poor glycemic control. Diabetic patients who have received renal allografts may have new glomerular lesions that are manifested structurally by increases in mesangial and glomerular volume. Successful pancreas transplantation produces long-term normoglycemia and provides a unique opportunity to evaluate the impact of the normalization of the blood glucose level on the development of the renal lesions typical of diabetes mellitus in transplanted kidneys. We obtained biopsy specimens from the functioning renal allografts of 12 patients with insulin-dependent (Type I) diabetes before successful pancreas transplantation (performed one to seven years after renal transplantation) and repeated the biopsy at least 1.9 years later. In renal biopsy specimens obtained before pancreas transplantation, the mesangial volume was normal or modestly increased and the glomerular basement membrane was moderately thickened. At follow-up, no progression could be detected in any structural measure in the glomerulus. Furthermore, the recipients of pancreas transplants had smaller glomerular volumes than 13 matched diabetic patients who were recipients of renal allografts but who did not undergo pancreas transplantation (means Â±SD, 1.80Â±0.55 vs. 2.47Â±0.73x106Î¼m3; P = 0.02) and showed markedly less mesangial expansion (mesangial-volume fraction, 0.19Â±0.07 vs. 0.31 Â±0.10 Î¼m3per cubic micrometer; P = 0.004). We conclude that successful pancreas transplantation is associated with significantly less severe diabetic glomerulopathy in kidneys previously transplanted into diabetic patients. These data support the hypothesis that normoglycemia can prevent the progression of diabetic glomerulopathy in humans. (N Engl J Med 1989; 321: 80-5.) THE relation between hyperglycemia and the microvascular complications of diabetes mellitus is controversial,1 2 3and much of the controversy revolves around the question of the adequacy of glycemic control.4 5Neither multiple insulin injections nor continuous subcutaneous insulin infusion has been able to normalize glycemia in the long term.6 7 8In diabetic patients who have received renal allografts, the development of new glomerular lesions is best illustrated by mesangial expansion, with increases in the size of glomeruli. The transplantation of either the whole pancreas or a segmental graft results in the prolonged normalization of glycemia in humans,9and the transplantation of islets both.Â .Â .