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In order to explore the establishment method of animal model with experimental high altitude cerebral edema rats, for the study the pathogenesis and treatment measures of high altitude brain edema to provide experimental basis.the rats exposed to 4000 in simulated high altitude hypoxia environment exhaustive exercise 2 days after placed in the 8000 m altitude exposed for 3 days, to establishment the model of acute experimental brain edema.Using dry and wet method for determination the water content of brain, Evans blue (EB) tracer method measuring permeability of BBB, HE staining observation the pathological changes of brain tissue, and transmission electron microscopic of lanthanum nitrate tracer to observation the ultrastructure of tight j unctions of BBB and brain tissue, immunohistochemical method and Western blot method for the detection the gene expression of occludin protein and claudin-5.Real-time fluorescent quantitative PCR assay for detection the gene expression of TJ associated molecular (ZO-1) and so on methods to evaluate the animal model.The results showed that the rats after exhaustive exercise 2 days under hypoxia put on the 8000 m exposure for 3 days, results showed that brain water content and Evans blue content are increased significantly (P<0.01).the neurons is destroyed serious, tight junctions between endothelial cell of brain microvascular is open, lanthanum nitrate particles diffuse leakage into the brain interstitial, capillaries around edema, brain interstitial edema is increased significantly.Expression of Occludin mRNA and protein levels in hypoxia group was lowest,expression of ZO-1 is decreased significantly (P< 0.05), claudin-5 were is lowed significantly.sodium aescinate treatment after cerebral water content is decreased significantly (P<0.05), EB leakage is reduced significantly, cellular edema decreased significantly, the lanthanum particles leakage of brain interstitial is reduce significantly, the degree of edema is reduced significantly, the expression of occludin mRNA and protein levels, ZO-1, claudin-5 gene expression are increased significantly (P<0.01).Conclusion: The rats exposure to acute hypoxic and exhaustive exercise can cause cerebral edema,sodium aescinate can reducing BBB permeability, significant to improve the brain edema under hypoxic exposure.