Abstract: OBJECTIVE To observe the protective effects of rose total flavonoids on cerebral ischemia reperfusion injury in mice. METHODS By using the suture block the left middle cerebral artery to establish the focal cerebral ischemia-reperfusion model in mice. Nimodipine group, Nao Luo Tong group, the high, medium and low dose of rose total flavonoids groups were given related drugs via intragastric administration before the operation. The sham operation group, and ischemia-reperfusion group were given the same volume of 0.5% sodium carboxymethyl cellulose for seven days, once a day. One hour after the last administration model, after operation sober, evaluating neural function score of mice, reperime 22 h, measuring the concentration of S-100β in serum, TTC stained of brain tissue slices, calculating the area of cerebral infarction. RESULTS Rose total flavonoids groups significantly decreased the nerve function score in mice, reduced the area of cerebral infarction in mice, significantly decreased the content of S-100β protein in serum, significantly improved the pathological changes of cortical areas in brain tissue. CONCLUSION Rose total flavonoids could inhibit S-100β in serum released after cerebral ischemia reperfusion injury, improve the nerve injury symptoms, reduce the infraction area of brain and improve the pathological changes of cerebral cortex, thereby rose total flavonoids play a protective role on cerebral ischemia reperfusion injury.