Objective To investigate the protective effect and mechanism of crocetin on focal cerebral ischemiareperfusion injury. Methods 120 SD rats were divided into six groups, named as sham operation (sham group), model control of cerebral ischemiareperfusion injury (model group), nimodipine positive control(Nim group), high dose of crocetin group(40 mg8226;kg-1), moderate dose of crocetin group(20 mg8226;kg-1), low dose of crocetin group(10 mg8226;kg-1). The sham group and model group were given with the same dose of normal saline. The rats were treated once in each group in the morning by reperfusion for a week. The model of neurological deficits was made by 2 h of middle cerebral artery occlusion followed with 22 h reperfusion. To observe the nerve functional defect score, cerebral infarction, and check the content of malondialdehyde (MDA), nitrogen monoxidum oxide (NO) and activity of superoxide dismutase(SOD) in ischemic brain tissues. Results The nerve functional defect scores of high, moderate and low dose of crocetin group, Nim group, sham group and model group were (0.35±0.31), (1.21±0.54), (2.04±0.32), (1.29±0.42), (0.00±0.00), (2.12±0.64), respectively; volume ratio of cerebral infarction were (13.2±4.3)%, (21.6±3.5)%, (34.2±2.7)%, (20.6±4.2)%, (0.0±0.0)%, (44.8±3.2)%, respectively; the content of MDA were (2.0±0.5), (2.9±0.4), (3.8±0.7), (2.5±0.8), (2.1±0.6), (4.2±0.7) μmol8226;g-1, respectively; the content of NO were (5.8±1.5), (8.8±1.3), (10.8±2.3), (8.8±2.1), (6.3±1.1), (12.8±1.3) μmol8226;g-1, respectively; the activity of SOD were (198.3±13.1), (159.8±10.9), (132.4±12.1), (164.3±10.7), (202.6±12.5), (121.1±11.6) kU8226;g-1, respectively.Crocetin improved cerebral infarction and nerve function, enhanced SOD activity, reduced MDA and NO content in a dosedependent manner. Conclusion Crocetin can protect focal cerebral ischemiareperfusion injury, the mechanism of which may be related to SOD activity enhancement and reduction of MDA and NO levels.