Objective: To discuss the expression and significance of NALP3 (NACHT-LRR-PYD- containing protein3) inflammasome in SD rats of acute lung injury in simulated hypoxic environment. Methods: Forty SD rats were randomly divided into 4 groups: control and 1, 3, 7 d groups respectively. The rats kept in hypoxic chamber which simulated the environment of 5 000 m altitude for 1, 3, 7 days. After that, the rats were sacrificed and lung tissues were obtained. Meanwhile we examined the arterial blood-gas, wet/dry mass ratio of lung tissues, and the pathological and ultrastructural changes of lungs were also been detected. At last, the protein expression levels of NALP3, caspase-1and IL-1β were analyzed by immunohistochemical method, the serum level of IL-1βwas tested by ELISA assay. Results: The lung inflammation scores in actue injury groups were significantly higher than those in control group (P<0.05). The 3 day group was the highest than those in 1 d, 7 d groups (P<0.05). In the electron microscope, there were physalides in cytoplasm of AT II cell in study group, and there were many macrophages in the alveolar cavity were observed. Expressions of NALP3, caspase-1 and IL-1β were increased from the first day at the same time, and reached the peak levels in the third day, but decreased from the seventh day, those trends were positively correlated with the degree of lung injury. The serum level of IL-1β was higher in study group than that in control group, but the 3d group is the highest in the study group (P<0.05). Conclusion: At the early stage of hypoxic acute lung injury, the NALP3 inflammasome is activated through caspase-1 pathway, and which increased the release of IL-1β and lead to the pathogensis of lung injury, our result suggests that NALP3 inflammasome may play an important role in the occurrence and development of the acute lung injury exposed in high altitude.