Traumatic brain injury (TBI) is a worldwide health problem with oxidative stress recognized as a major pathogenetic factor, and leading cause of disability and death in young adults. The present experimental work was designed to study the role of oxidative stress in TBI. Mice were randomly classified into two groups (Sham group and TBI group, n=18 each). Mice were anaesthetized with chloralhydrate (400mg/kg), after 24 hour of the surgery, the animals were killed by cervical dislocation, and brains were rapidly isolated and homogenized in saline, sham animals were subjected to same conditions without TBI. Traumatic brain injury group exhibited significant increment in lactate dehydrogenase (LDH), malondialdehyde (MDA) and prostaglandin E2 (PGE-2) contents as compared to sham group. Also, TBI group showed decrease in total antioxidant capacity (TAC) and systolic blood flow (SBF). TBI group showed focal gliosis detected in the cerebral cortex, associated with neuronal degeneration and diffuse gliosis in the striatum of the cerebrum. Based on our results, we concluded that, increasing oxidative stress plays an important role in TBI and decreasing it will offer neuroprotection to mice against TBI