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Objective To investigate the possibility of applying hyperbaric oxygen preconditioning(HBO-PC)to reduce or prevent high-altitude pulmonary edema(HAPE)and to detect whether aquaporin 5(AQP5)are involved in HAPE pathogenesis.Methods Thirty eight rats were divided into three groups:the control,the HBO-PC and the HAPE groups.Western blot and real-time PCR were used to analyze the expression of AQP5 in the lungs.The wet-to-dry weight ratio(W/D weight ratio)and morphology of the lung were also examined.Results Lung W/D weight ratio in the HAPE group(4.36±0.53)compared with that of the control group(3.90±0.15)(P＜0.05),were marked interstitial edema in all the lung sections in the HAPE group,and fewer changes in 10 of 13 sections in the HBO-PC group.Lung-injury scores of the HBO-PC group were much lower than those of the HAPE group.AQP5 of the HAPE group decreased significantly at the protein and gene levels compared with those in the control group(P＜0.01,P＜0.05).Protein and mRNA expression of AQP5 in the HBO-PC group were much higher than those of the HAPE group(P＜0.05,P＜0.01).Lung injuries in the HAPE rats were related positively to the AQP5 expression in the lung(protein expression r=-0.635,P＜0.01;mRNA expression r=-0.399,P＜0.05).Conclusions We concluded that HBO-PC could alleviate lung injury in rats caused by high-altitude hypobaric hypoxia and reduce HAPE incidence.HAPE in rats was associated with the down-regulation of expression of AQP5 in the lungs.This down-egulation could be attenuated by HBO-PC.This study is the first one introducing HBO-PC in the prevention of HAPE,and the first investigation on the expression of AQP5 in a rat model of HAPE.