This study was designed to investigate the effects of chronic toluene inhalation in high concentration on lipid peroxidation, antioxidant enzyme activities and ultrastructural changes in the sciatic nerves of rats. Male Wistar albino rats (150-250 g) were divided in two experimental groups: the control and the toluene treated group (n=10 for each). Toluene treatment was performed by inhalation of 3000 ppm toluene, in a 8 h/day and 6 day/week order for 16 weeks. Blood and tissue samples were obtained for biochemical and histopathological investigation. The blood and sciatic nerves were assayed for toluene by gas chromatography. Toluene significantly increased blood and tissue malondialdehyde (MDA), and decreased tissue superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but not tissue catalase (CAT) levels when compared with controls. Electron micrographs of sciatic nerve in the toluene group shows myelin destructions with onion-bulb and bubble form protrusion on the myelin sheath and axolemma border of myelinated axons. The area of injury on the myelin sheath were measured by Image-Pro Plus. Mean of the injury area were estimated 34% each myelin. These findings indicate that chronic toluene inhalation might be involved with free radical processes.