Objective To establish a rat model simulating high-altitude pulmonary edema by using hypobaric chamber. Methods Sixty healthy Wistar rats (male:female=1:1) were randomly divided into five groups: control group, hypoxia 24 h group, hypoxia 48 h group, hypoxia 72 h group, and hypoxia 7 d group. Except for the control group, hypoxia group rats were put in hypobaric chamber for the given time. The lung water content, contents of IL-6 and TNF-α in the lung homogenates were assessed and histological examination was conducted on all animals. Results Compared with the control group, the lung water content, content of IL-6 and TNF-α in the lung homogenates were significantly increased in the hypoxia 24 h group, hypoxia 48 h group and hypoxia 72 h group, while lung water content, content of IL-6 and TNF-α in the lung homogenates were lower than that in the hypoxia 72 h group. Interstitial pulmonary edema and inflammatory cell infiltration, alveolar septal widening and interstitial hyperemia were found in the hypoxia 72 h group. Conclusion A rat model of high altitude pulmonary edema is successful set up by putting the rats in hypobaric chamber for 72 h.