The purpose of this study was to determine if alpha-tocopherol-a reactive oxygen species (ROS) scavenging agent-inhibits LPS-induced oxidative stress and interleukin-6 (IL-6) production in murine microglia and brain. LPS increased intracellular peroxides and IL-6 in a dose-dependent fashion in primary microglia. The LPS-induced increase in ROS and IL-6 was reduced by pretreatment of alpha-tocopherol. Intraperitoneal injection (i.p.) of LPS induced lipid peroxidation and IL-6 in brain. Importantly, three daily injections (20 mg) of alpha-tocopherol increased brain alpha-tocopherol and decreased LPS-induced lipid peroxidation and IL-6 in brain. Taken together, these data indicate that alpha-tocopherol can mitigate inflammatory cytokine production in the brain.