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Mao Dongqing (MDQ) is the dried root of Ilex pubescens Hook. et Arn. It is a renowned traditional Chinese medicine which has been used for the treatment of acute and chronic cardio-cerebrovascular diseases in the clinic for many years. The aim of this study was to further understand the effect of total flavonoids from MDQ on cerebral ischemia reperfusion injury.Ginaton group (extract of ginkgo biloba leaves injection), the small, middle and large doses of total flavonoids from the MDQ group were given related drugs via intragastric administration before the operation. The sham operation group, ischaemic preconditioning model group and ischemia reperfusion group were given the same volume of 0.1% CMC daily for 10 days. After the last administration, animal models of cerebral ischemia reperfusion injury in mice were established using the method of blocking the bilateral common carotid artery for 10 min, restoring perfusion for 10 min, bilateral carotid artery occlusion for 10 min, and then reperfusion for 24 hours. Half of the brain was fixed in 10% formalin for HE staining. The other half of the brain was used to prepare brain homogenate, which was used to determine the content of ATPase, NO and NOS.We found that the models with cerebral ischemia reperfusion injury in mice were copied successfully. Large and medium doses of total flavonoids from MDQ could significantly reduce the content of NO, tNOS, iNOS and increase the activity of ATPase in brain tissue of mice. Total flavonoids from MDQ could also reduce the pathological changes of the hippocampus and cortical neuron cells in the hippocampus of mice.The results of this study showed that the model of cerebral ischemia-reperfusion in mice was successful. The total flavonoids from MDQ could achieve the role of anti-cerebral ischemia injury by inhibition of the inflammatory cascade, improving the imbalance of oxygen supply and demand and the disorder of glucose metabolism, inhibiting the apoptosis of nerve cells during cerebral ischemia reperfusion injury.National “Significant New Drug Creation” science and technology major special project (2009Z × 09103-324).