Abstract: Objective To explore the regulation of hypothalamic-pituitary-thyroid (HPT) axis hormone secretion, vascular endothelial growth factor (VEGF) expression in different hypoxic conditions and their relationships with high altitude pulmonary edema. Methods Ninety-six Wistar rats were randomly divided into four groups, 1 500 m (control), 3 500 m, 5 000 m and 6 000 m group. Then, rats in each group were divided into hypoxia 12 h subgroup, 24 h subgroup and 48h subgroup with totally 12 groups and 8 rats in each group. Rats in control group were kept in department of animal experiment (Lanzhou at an altitude of 1 500 m), and rats in other hypoxia groups were put in hypobaric chamber simulating different altitude and underwent hypoxia exposure for 12 h, 24 h and 48 h. After separating lung tissues, the water contents in lungs of rats were determined by dry-wet proportion method, and histopathologic changes were observed with HE staining. The contents of TRH, TSH, T3, T4 in serum were determined with ELISA. The expression of HIF-1mRNA and VEGF mRNA were detected by real time PCR. Results Compared with control group, the water content of lung tissues in rats increased in hypoxia groups. The main hormone indicators of HPT axis (TSH, T3, T4) decreased and TRH increased with the increase of altitude in hypoxia groups (P＜ 0.05). The expression of HIF-1 mRNA and VEGF mRNA also increased with the increase of altitude in hypoxia groups (P＜ 0.05). Conclusion With the increase of altitude, HPT axis is suppressed. The level of VEGF also increases and it is closely related to high altitude pulmonary edema, which suggests that HPT axis may play a key role in regulating the high altitude pulmonary edema.