Luteolin recently has been proved to elicit a vanity of biological effects through its antioxidant and anti-apoptosis properties. Oxidative and apoptosis damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The aim of this study was to evaluate the neuroprotective effects of luteolin and the underlying mechanisms in cerebral ischemia. Focal cerebral ischemia was induced in adult male Sprague-Dawley rats by permanent middle cerebral artery occlusion (pMCAO). Luteolin was injected intraperitoneally at different doses of 10 or 25 mg/kg immediately after pMCAO. Experiment 1, luteolin's neuroprotective effect was analyzed. Neurological deficits, brain water content and infarct volume were evaluated at 24 and 72 h after pMCAO. SOD1, Bcl-2, and Bax expression were measured by immunohistochemistry, western blot and reverse transcription-polymerase chain reaction. Experiment 2, luteolin's anti-oxidative activities were evaluated. SOD1, CAT activities, and MDA content were measured by spectrophotometer. Experiment 3, the influence of luteolin on claudin-5 was detected. Compared with MCAO group, luteolin significantly increased the activities of SOD1, CAT, Bcl-2 and claudin-5 (P < 0.05), decreased the levels of MDA and Bax (P < 0.05), and alleviated the neurological deficits, infarct volume and brain water content (P < 0.05). The results indicated that luteolin protected the brain from ischemic damage, and this effect may be through reduction of oxidative stress and apoptosis, and upregulation of the expressions of claudin-5.