Introduction Oxcarbazepine(OXC), a voltage-gated sodium channel blocker, is a new antiepileptic medication. OXC is also used for the treatment of bipolar disorders. In this study, we investigated the protective effect of OXC and its mechanisms in the cornu ammonis 1subfield (CA1) of gerbils subjected to 5min of transient global cerebral ischemia (tGCI). Material & Method Transient ischemia led to death of most pyramidal neurons in CA1 at 5days after tGCI. OXC (100 and 200mg/kg) was intraperitoneally administered once at 30 min after tGCI. Result Treatment with 200mg/kg OXC, not 100 mg/kg OXC, significantly protected CA1 pyramidal neurons from tGCI-induced injury. OXC treatment significantly decreased superoxide anion production, 4-hydroxy-2-nonenal and 8-hydroxyguanine levels in ischemic CA1 pyramidal neurons. In addition, the treatment restored levels of superoxide dismutases, catalase, and glutathione peroxidase. Furthermore, the treatment distinctly inhibited tGCI-induced microglia activation and significantly reduced levels of pro-in?ammatory cytokines (interleukin-1β and tumor necrosis factor-α). Conclusion OXC treatment significantly enhanced expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream protein heme oxygenase-1 in ischemic CA1; however, the forenamed effects of OXC were abolished by brusatol (an inhibitor of Nrf2).