BACKGROUND Since peripheral nerves are damaged in diabetes mellitus, morphological changes occur within the diabetic muscle in response to the diabetic neuropathy. The aim of this study was to examine the extensor digitorum longus (EDL) from a 42-day streptozotocin-induced diabetic Swiss Webster mouse (STZ) and compare the muscle morphology and histochemistry to age-matched, nondiabetic controls. METHODS The EDL was evaluated using electron microscopy in order to investigate the morphological integrity of the myofibers and neuromuscular junctions. Histochemical analysis was completed using the myofibrillar CA(++)-ATPase reaction of Doriguzzi et al. (1983. Histochemistry, 79:289-294) for use in computer-assisted morphometric analysis of fiber size using Bioquant System 4 software. RESULTS Ultrastructural analysis of the diabetic EDL (N = 5, 225 myofibers/animal) showed a significant number of abnormal myofibers, exhibiting various degrees of degeneration, signs of denervation, and necrosis. The STZ myofibers exhibited excessive lipid accumulations and abnormal mitochondrial arrangements. Histochemical analysis of the STZ EDL revealed a significant shift in fiber type profile (53.6% type 2A and 46.4% type 2B- STZ myofibers; 47.5% type 2A, 52.5% type 2B nondiabetic controls). Morphometric analysis of myofiber size by fiber type (200 myofibers/muscle/fiber type) indicated a significant decrease in myofiber size for both type 2A and type 2B fibers in the STZ diabetic mouse. CONCLUSIONS The degeneration and necrosis of myofibers concomitant with the sever atrophy of both the type 2A and 2B myofibers in the STZ muscle could account for the functional alterations seen in diabetic muscle.