To establish hypoxic-ischemic encephalopathy (HIE) model on C 57 BL/6 mice by carotid artery ligation and hypoxia inhalation, and to observe the effect of Rongshuan Capsules. Methods: C 57 BL/6 mice were randomly divided into 5 groups: sham-operation group, model group, large dosage of Rongshuan Capsules, middle dosage of Rongshuan Capsules, and small dosage of Rongshuan Capsules (400 mg/kg, 200 mg/kg and 100 mg/kg). HIE model mice were established by left carotid artery ligation on C 57 BL/6 mice and hypoxia inhalation (O2:N2 = 8:92) for 15 minutes. Intragastric administration was used on HIE model mice 24 hours after ischemia anoxic damage, 1 time/day and consecutively treated for 4 weeks. After 4 weeks of treatment, muscle strength, ability of learning and memory, NSE, MAP-2 and Caspase-3 expression and the brain tissue pathomorphological changes were tested. Results: Four weeks after model establishment, muscle strength and learning and memory ability of HIE model mice were decreased significantly. MAP-2 and NSE expression was down-regulated, and Caspase-3 expression was up-regulated. Pathological examination showed that neurons were arranged in disorders, large amount of degenerated, necrotic and apoptotic cells. Large pieces of softening lesion, expansion and congestion of vessels and inflammatory cell infiltration were also observed. Rongshuan Capsules improved these indexes significantly in drug administration groups. Conclusion: Caroted artery ligation with hypoxia successfully established HIE models on C 57 BL/6 mice. Rongshuan Capsules facilitated model mice of muscle strength and learning and memory ability as well as MAP-2 and Caspase-3 expression, release the pathological injury of brain tissues, whose mechanism may be related to its neural protection.