AIM To study protective effects of scutellarin (SCU), a flavonoid from a traditional Chinese medicinal plant, on brain damage in rats after ischemia-reperfusion (I-R) injury, and to investigate different interventions of SCU and SCU time-effect relationship.METHODS Transient cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1 h followed by 24 h reperfusion in rats.Neurological deficit scores and brain infarction volume were measured 24 h after reperfusion, histopathological changes for HE staining was observed to certify the protective effects of SCU.RESULTS The neurological scores of SCU 45 mg·kg-1 were significantly decreased compared to that in model group.The infarct volume were significantly decreased by administration of SCU.The edema volume of SCU 45 mg·kg-1 group were significantly decreased.The histopathological changes in each treated group of SCU were significantly gentler than model group.The concentration of vWF in plasma was reduced while the concentration of t-PA was increased by administration of SCU.SCU pre-treatment, post-treatment and treatment during I-R showed protection on brain I-R damage, of which the treatment during I-R was most effective.The protective effects of SCU on brain I-R injury were observed continuously 1-7 d after SCU treatment.The infarct volume of SCU 45 and 180 mg·kg-1 group were significantly decreased on 1, 3,7 d after reperfusion.Along with the length of reperfusion, infarct area of SCU 45 mg·kg-1 group and model group were all in a trend of decline.CONCLUSION SCU (45-180 mg· kg-1, iv)treatment showed significantly protective effect on cerebral I-R injury in rats by markly reducing the infarct range and neurological deficit scores.SCU pre-treatment, post-treatment and treatment during I-R reduced rat brain I-R damage.The rat cerebral I-R injury has a trend of restore, the protective effects of SCU 45 mg·kg-1 on rat brain I-R injury were observed between 1-7 d after SCU once treatment.