Abstract: Objective To explore the expression of lung Aquaporin5 (AQP5) in premature rats and after inhaling hyperoxia. Methods Gestation 21 day Sprague-Dawley(SD) fetuses (term=22 day) were randomly assigned to control group and hyperoxia group within 12h～24 h after birth. Hypreoxia group was exposed to about 85% oxygen and control group in room air. After 1 to 14 days of exposure, lung tissue was extracted and AQP5 mRNA was detected by RT-PCR. Immunohistochemistry and western-blot were used to detect AQP5 protein. Results The expression of lung AQP5 in premature rats increased persistently after birth, and the positive staining was restricted to the typeⅠalveolar epithelial cells. Compared with control group, the AQP5 mRNA in hyperoxia group of day 1 increased significantly (P <0.05 ), but after exposure to hyperoxia for 4 to 14 days, the AQP5 expression decreased remarkedly in mRNA and protein level (P <0.05 or P <0.01). Conclusion By regulating the lung water balance, AQP5 may play a key role in the alveolar period of premature rats. Hyperoxia down-regulated the AQP5 expression, this may be an important factor for the development of hyperoxia lung injury.