Objective To study the effect of oxymatrine on oxidative stress and inflammatory reaction after cerebral ischemia reperfusion in rat. Methods A total of 140 SD rats were randomly divided into the sham group, model group and oxymatrine low, medium, high-dose groups (28 in each group). Beyond the sham group, the other groups were established the rat model of focal cerebral ischemic reperfusion with Zea-Longa occluded suture. The the low-, medium- and high-dose matrine groups were given 25, 50, and 100 mg/kg oxymatrine solutions injected intraperitoneally from the second day after operation for 7d. , The model group and the sham group were injected with an equal volume of saline. The neurological deficits, ratio of infarct volume, water content of the brain were evaluated; the morphological changes of brain tissue were observed by HE Staining, and the cell apoptosis were observed after TUNEL staining; the activity of antioxidant enzymes and malondialdehyde (MDA) in brain tissue were measured by biochemical analysis; the content of NO and the activity of iNOS were measured; the expression of NF-ĸB were determined by Western blotting. The inflammatory cytokines in brain tissue were determinated. Results Compared with the model group, the neurological function score, brain tissue water content, infarct volume and apoptotic index decreased in the rats of oxymatrine medium-, high-dose groups (P<0.05 or P<0.01). The activity of SOD (148.68 ± 9.12 U/mg, 161.34 ± 10.09 U/mg vs. 140.63 ± 8.47 U/mg), CAT (3.90 ± 1.32 U/mg, 4.15 ± 1.47 U/mg vs. 2.73 ± 0.89 U/mg), GSH-Px (11.46 ± 2.65 U/mg, 13.59 ± 3.27 U/mg vs. 9.35 ± 2.03 U/mg) were significantly increased (P<0.05 or P<0.01). The content of MDA (20.18 ± 3.59 μmol/g, 17.46 ± 3.21 μmol/g vs. 29.86 ± 5.40 μmol/g), iNOS (12.64 ± 1.83 U/mg, 11.75 ± 1.62 U/mg vs. 14.17 ± 2.06 U/mg), NO (23.64 ± 2.18 μmol/g, 21.27 ± 2.03 μmol/g vs. 27.82 ± 2.42 μmol/g), TNF-α (43.9 ± 6.3 nmol/L, 37.2 ± 5.8 nmol/L vs. 56.3 ± 6.9 nmol/L), IL-1β (715.0 ± 68.5 nmol/L, 683.9 ± 70.8 nmol/L vs. 930.8 ± 91.4 nmol/L), IL-6 (168.4 ± 22.5 nmol/L, 133.7 ± 18.1 nmol/L vs. 212.5 ± 24.7 nmol/L) were significantly decreased (P<0.05 or P<0.01). The expression of NF-ĸB in brain (0.35 ± 0.13, 0.24 ± 0.08 vs. 0.62 ± 0.15) were significantly down-regulated (P<0.05 or P<0.01). Conclusions The Oxymatrine inhibits oxidative stress injury and inflammatory response after cerebral ischemia-reperfusion in rats. Key words: Matrine; Brain ischemia; Reperfusion injury; Oxidative stress; Inflammatory; Rats