Background: In patients with type 1 diabetes mellitus who do not have uremia and have not received a kidney transplant, pancreas transplantation does not ameliorate established lesions of diabetic nephropathy within five years after transplantation, but the effects of longer periods of normoglycemia are unknown. Methods: We studied kidney function and performed renal biopsies before pancreas transplantation and 5 and 10 years thereafter in eight patients with type 1 diabetes but without uremia who had mild to advanced lesions of diabetic nephropathy at the time of transplantation. The biopsy samples were analyzed morphometrically. Results: All patients had persistently normal glycosylated hemoglobin values after transplantation. The median urinary albumin excretion rate was 103 mg per day before transplantation, 30 mg per day 5 years after transplantation, and 20 mg per day 10 years after transplantation (P=0.07 for the comparison of values at base line and at 5 years; P=0.11 for the comparison between base line and 10 years). The mean (±SD) creatinine clearance rate declined from 108±20 ml per minute per 1.73 m2 of body-surface area at base line to 74±16 ml per minute per 1.73 m2 at 5 years (P<0.001) and 74±14 ml per minute per 1.73 m2 at 10 years (P<0.001). The thickness of the glomerular and tubular basement membranes was similar at 5 years (570±64 and 928±173 nm, respectively) and at base line (594±81 and 911±133 nm, respectively) but had decreased by 10 years (to 404±38 and 690±111 nm, respectively; P<0.001 and P=0.004 for the comparisons with the base-line values). The mesangial fractional volume (the proportion of the glomerulus occupied by the mesangium) increased from base line (0.33±0.07) to 5 years (0.39±0.10, P=0.02) but had decreased at 10 years (0.27±0.02, P=0.05 for the comparison with the baseline value and P=0.006 for the comparison with the value at 5 years), mostly because of a reduction in mesangial matrix. Conclusions: Pancreas transplantation can reverse the lesions of diabetic nephropathy, but reversal requires more than five years of normoglycemia.