Abstract: Objective To study the preventive effect of acetazolamide（AZ） on high-altitude pulmonary edema（HAPE） in rats and its possible mechanism. Methods Male Wistar rats were randomly divided into control group,AZ group,and placebo group.A rat HAPE model was established.Five days after the rats were interfered with AZ at the dose of 100mg/（kg.d）,the wet/ dry（W/D） ratio,protein concentration in bronchoalveolar lavage fluid（BALF）,pulmonary edema and hemorrhage score,nitric oxide（NO） level and NO synthase（NOS） activity in serum and lung tissue of rats were measured. Results The W/D ratio,protein concentration of BALF,pulmonary edema and hemorrhage score were significantly higher in placebo group than in control group（P＜0.05） and significantly lower in AZ group than in placebo group（P＜0.05）.The NO level and NOS activity in serum and lung tissue were significantly lower in placebo group than in control group and significantly higher in AZ group than in placebo group（P＜0.05）. Conclusion Administration of AZ for 5d can effectively prevent HAPE in rats by up-regulating NO level and NOS activity in serum and lung tissue.