Diabetic neuropathy (DN) is a frequent, serious and debilitating chronic complication of diabetes mellitus (DM). Hyperglycemia, oxidative and nitrosative stress are involved in causing nerve damage in several animals, humans and experimental models of diabetes. This study was designed to investigate the synergistic cumulative neuroprotective effect of quercetin administration and moderate exercise training on sciatic nerves injuries in streptozotocin (STZ)-diabetic rats. DM was induced in Wistar rats by intraperitoneal administration of STZ (60 mg/kg). The diabetic rats received quercetin (30 mg/kg body weight/day) and performed an exercise training program (30 minutes/day, 5 days/week) for 5 weeks. Various biochemical parameters of oxidative and nitrosative stress were determined and histopathological evaluations were performed from sciatic nerves. Diabetic rats showed significantly increased oxidative and nitrosative stress parameter levels in the sciatic nerves. Diabetic trained rats treated with quercetin exhibited a significantly reduced hyperglycemia and its metabolic abnormalities induced by intraperitoneal administration of STZ. Histological alterations of the sciatic nerves induced after STZ administration were restored by administration of quercetin. Quercetin administration in association with moderate exercise training not only attenuated the diabetic condition but also restored sciatic nerves injuries by controlling hyperglycemia to down-regulate the generation of free radicals, as well as the elevation of antioxidant enzymes.