In order to explore whether hypobaric hypoxia exposure time and transplantation of plateau pika and plateau zokor intestinal flora will affect the expression of beta-amyloid protein (Aβ), tau and brain-derived neurotrophic factor (BDNF) in hippocampus of the Sprague-Dawley (SD) rats, SD rats were first randomly di-vided into normoxia group, hypobaric hypoxia group and hypobaric hypoxia treatment group. The rats in the hypobaric hypoxia group were further divided according to the exposure time (1, 3, 7, 15, and 28 days) to hy-pobaric hypoxia, while those in the hypobaric hypoxia treatment group were further divided according to the treatment factors: hypobaric hypoxia (as a control), hypobaric hypoxia + antibiotic treatment, hypobaric hypo-xia + antibiotic + zokor fungus treatment, hypobaric hypoxia + antibiotic + pika fungus treatment, hypobaric hypoxia + antibiotic + SD rat fungus treatment. Therefore, there were totally 11 groups, each having 10 rats. The morphological changes of hippocampal neurons in normoxia group and hypobaric hypoxia group were observed by Nissl staining. The expression levels of Aβ, tau and BDNF proteins in each group were detected by Western-blot. The results showed that, compared with the normoxia group, the hypobaric hypoxia group had loosely arranged and disordered neurons in the hippocampal CA1 area from the third day, with obvious nuclear condensation appearing in a time-dependent manner. The levels of Aβ and tau proteins were signifi-cantly increased from the 7th and 3rd days, respectively, of hypobaric hypoxia exposure, and further increased with the time of exposure, especially the level of tau protein. The BDNF protein level increased sig-nificantly in the early stage of hypobaric hypoxia exposure, and then decreased gradually with the exposure time, showing a significantly negative correlation with the Aβ and tau protein levels. In addition, compared with rats in antibiotic treatment group, rats transplanted with intestinal flora of plateau pika had significantly decreased expression of Aβ and tau proteins and significantly increased expression of BDNF in the hippo-campus under hypobaric hypoxia. The results revealed that hypobaric hypoxia could up-regulate the expression of Aβ and tau proteins and down-regulate the expression of BDNF protein in hippocampus of rats, and that intestinal flora transplantation could up-regulate the expression of BDNF protein in hippocampus of rats in a hypobaric hypoxic environment and also affect the expression of Aβ and tau protein. Transplantation with plateau pika intestinal flora down-regulated the levels of Aβ and tau proteins, while transplantation with plateau zokor intestinal flora up-regulated the level of tau protein and down-regulated the Aβ protein.