OBJECTIVE: Exposure to high concentrations of oxygen may impair the pulmonary development in premature neonates and ultimately result in chronic lung disease (CLD). But its precise mechanism has not been identified. This study aimed to investigate the role of alveolar epithelial type Ⅱ cells (AECⅡ) apoptosis and its signaling pathways in the development of hyperoxia-induced CLD in premature rats. METHODS: Ninety-three premature newborn rats were randomly assigned into a Control group (exposed to air,n = 45) and a Model group (exposed to ≥95% O_2,n = 48). Apoptosis and relative factor expression were determined with the terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL), electron microscopy, and reverse transcriptase PCR (RT-PCR). RESULTS: The apoptotic index increased in the Model group from day 7 to day 21 of hyperoxia inducement(P <0.05). The apoptotic cells were AECⅡ. Bax mRNA levels in the Model group were higher than those in the Control group after the 3rd day(P <0.05), while Bcl-2 expression in the Model group was lower on the 7th, 14th and 21st days than that in the Control group(P <0.05). There was no difference in the Fas mRNA expression between the two groups. CONCLUSIONS: Apoptosis of AECⅡis present in the process of hyperoxia-induced CLD and may be one of major causes of poor alveoli development related to hyperoxia-induced CLD . The changes in the Bax and Bcl-2 ratio may be involved in the initiation of the signaling pathway of AECⅡapoptosis, while Fas transcriptional expression may be irrelevant.