The effect of pancreatic islet transplantation on the development of diabetic myopathy in streptozotocin-induced diabetic Lewis rats was examined histochemically and morphometrically in a proximal striated (rectus femoris) muscle. Diabetes was induced by streptozotocin administration, and diabetic animals were transplanted by intraportal grafts 6 weeks later. Islet-transplanted rats returned to euglycemia usually within the first 24 hours after transplantation and remained euglycemic over the subsequent 12-week observation period. Transplanted animals were compared with age-matched nontransplanted diabetic rats and nondiabetic age-matched control rats. Successful isotransplantation completely prevented the characteristic fast twitch (type IIB, glycolytic) fiber atrophy and also the changes in the fiber-type relative percentages, with prevention of the significant increase in the frequency of slow twitch oxidative (type I) and fast oxidative/glycolytic (type IIA) fibers at the expense of fast twitch glycolytic (type IIB) fibers. The histochemical appearance of all fiber types studied from muscles in transplanted rats was identical to equivalent fibers in age-matched control rats. Our data suggest that diabetic muscle pathology could be reversed and the progression of diabetic amyotrophy halted through the restoration of a euglycemic state by successful pancreatic islet transplantation, at least in short-term experimental diabetes.