Pancreas transplantation (PTx) is the only available treatment which is able to restore normoglycemia without exposing patients to the risks of severe hypoglycemia, thus allowing testing the effects of very long-term euglycemia in preventing, halting and reversing diabetic nephropathy (DN). Pancreas and islet transplantation in animal models have been shown to prevent, ameliorate or reverse the development of DN lesions. PTx, performed simultaneously or shortly after kidney transplantation in patients with type 1 diabetes prevents the recurrence of diabetic glomerulopathy lesions in the renal allograft. To test whether DN lesions are reversible in humans, we studied renal structure before and 5 and 10 years after PTx in nonuremic patients with long-term type 1 diabetes, with mild to advanced DN lesions at baseline. Diabetic glomerular lesions were not significantly changed at 5 years after PTx, but were markedly improved after 10 years. Indeed, in most patients glomerular structure had returned to normal at 10-year follow-up. These pancreas transplant studies also showed that remodeling of the tubulointerstitium and decrease in interstitial collagen was possible. Thus, the lesions of DN are reversible by long-term normoglycemia, and that it is possible in humans associated with substantial architectural remodeling and healing of glomerular, tubular, and interstitial structures.