Objective To simulate the process of hypoxic-ischemic brain injury at high altitude in a simulated cabin with plateau low pressure environment, and to prepare a rat model of cerebral injuries at different high altitudes. Method Thirty-two 0-day-old neonatal SD rats were divided into four groups, namely group A (control group) and three test groups:group B (2000 m group), group C (4000 m group), and group D (6000 m group). The rats of control group were reared in a barrier environment. The rats of test groups were placed in a simulated cabin with plateau low pressure environment, and to prepare neonatal cerebral ischemia-hypoxia model by sport activities. The sport movements were carried out in the cabin in a swimming groove 60 min/d, and not less than 20 hours a day at high altitude low pressure environment. Zea Longa 5 point scale standard was used to determine the behavioral scores at the 3th 7th 11th 15th days, and samples were collected on the 15^th day to observe red blood cell morphology using HE and 2,3,5-triphenyltetrazolium chloride (TTC) staining and ultrastructure by scanning electron microscopy.Result (1) The neurological scores of the test groups A, B, C were significantly different from that of the control group (P<0.05), and the scores of test group D and control group were very significantly different (P<0.01). (2) The histopathological examination using HE staining showed inflammatory cell infiltration in all rats of the test groups, and the extent of inflammatory cell infiltration was positively correlated with the increase of altitude. (3) The histopathology with TTC staining revealed prominent ischemia in the cerebral cortex of rats in the plateau hypoxic environment. (4) Scanning electron microscopy showed that the rat erythrocytes were cap-like in the group B, irregular in the group C, and zigzag shape in the group D. Conclusions In this study, a rat model of neonatal hypoxic-ischemic encephalopathy (HIE) is successfully established by hypoxic cabin combined with sport activity. This model is stable, reliable, more closely mimicking the pathogenesis and clinical manifestation of neonatal HIE than models prepared with other methods, therefore, may be used in related research.