AIM: To compare the formation and release of neutrophil extracellular traps (NETs) after exposure to the high-altitude hypoxic environment for different periods, and their relationship with the dynamic changes of microcirculatory disorders associated with pulmonary edema. METHODS: SD rats were raised under normoxic conditions at an altitude of 400 m and under hypoxic conditions at an altitude of 4 200 m. The rats raised under hypoxic conditions at an altitude of 4 200 m for 7 days were returned to normoxic conditions at 400 m to observe the changes in physiological and pathological indicators of the rats. The dynamic changes of neutrophil extracellular traps (NETs) release and microcirculatory disorders related to pulmonary edema after high-altitude hypoxia exposure and after returning to the plain were explored by blood routine determination, rat arterial blood gas analysis, ELISA experiment, lung water content determination, H&E staining, and immunohistochemical staining. RESULTS: In the hypoxic environment at 4 200 m, rats exhibited significant reductions in arterial oxygen saturation (SaO2) and partial pressure of oxygen (PO2) (P<0.01), accompanied by a marked increase in lung-tissue water content (P<0.01). The complete blood count revealed elevated levels of red blood cells, white blood cells, lymphocytes, and neutrophils (P<0.01). In addition, the formation and release of NETs in neutrophils increased, accompanied by an aggravation of the inflammatory response. After returning to the low-altitude normoxic area at 400 m, the above indicators gradually returned to normal levels on the 7th day. Pathological changes such as alveolar epithelial cell shedding and inflammatory cell infiltration were observed in the lung tissues of rats in the high-altitude area, and the pathological changes were restored after returning to the low-altitude normoxic environment. CONCLUSION: The release of NETs from neutrophils is closely related to the recovery of pulmonary edema and pulmonary edema-related microcirculatory disorders after high-altitude hypoxia exposure.