OBJECTIVE To investigate the protective effect of hyperin (Hyp) on focal cerebral ischemia reperfusion injury in rats. METHODS Sixty Wistar male rats were randomly divided into sham-operated group, untreated group, and high-, medium- and low-dose Hyp-treated groups (50, 25 and 12.5 mg x kg(-1) x d(-1)) and ginkgo leaf-treated group. The animals were intragastrically administered with drugs for 5 days. Thirty minutes after the end administration, the operation was performed to induce the middle cerebral artery occlusion (MCAO) model in rats with the method of intraluminal thread. The middle cerebral artery blood flow was blocked for 2 hours, and then reperfused. Twenty-four hours later, the rats' neurology score was observed. Brain triphenyltetrazolium chloride (TTC) staining and dried wet method were carried out to measure the infarct size and the water content of rat brain tissue respectively. RESULTS The above-mentioned indexes in the untreated group showed significant differences compared with those in the sham-operated group (P<0.01).The infarct sizes of rat brain tissue in the high- and medium-dose Hyp-treated groups were obviously decreased compared with that in the untreated group (P<0.01, P<0.05). The water content of rat brain and the neurology score were also obviously reduced compared with those in the untreated group (P<0.05 or P<0.01). CONCLUSIONS Hyp could obviously reduce the brain infarct size and cerebral edema degree in focal cerebral ischemia reperfusion injury rats. Hyp has significant protective effect on focal cerebral ischemia reperfusion injury.