The aim of this study was to examine the effects of Hippophae rhamnoides extract (HRE), known to have antioxidant properties, on ischemia reperfusion-induced brain injury in rats. Eighteen albino Wistar male rats were divided into three equal groups: 15 min of brain ischemia-3 h of reperfusion (BIR) group, 50 mg/kg HRE + brain ischemia-reperfusion (HRE + BIR) group, and control group for sham operation (SHAM). Malondialdehyde (MDA) level, myeloperoxidase (MPO) activity and 8-OHdG levels significantly increased, whereas total glutathione (tGSH) level, glutathione reductase (GSHRd), glutathione s-transferase (GST) activities decreased in the brain tissues of BIR group compared to SHAM group. HR application reversed these changes and brought the levels closer to the level of SHAM group. This study has revealed that HR inhibits IR-induced oxidative damage and inflammation in rat's brain biochemically and it is effective in maintaining antioxidant activity and protecting against DNA damage in the tissue.