Abstract: Objective 　To study the change of the pulmonary surfactant protein C, D (SP-C, SP-D) and apoptosis of alveolar epithelium cells in neonatal rats with hyperoxia-induced lung injury. Methods　The neonatal rats born within 24 hours were divided into the air group (n=50) and the hyperoxia group (n=50). The lung tissue was collected on the first, third, seventh, tenth, fourteenth day after the hyperoxia exposure. The pathological changes were observed by HE staining. The apoptosis rate of lung epithelial cells was detected by TUNEL (terminal deoxyn ucleotidyl transfer-mediated end labeling). The content of SP-C and SP-D in broncho alveolar lavage fluid (BALF) was detected by enzyme-linked immunosorbent assay. Results　In the air group, as age increased, the alveolar were gradually more completely formed with the regular shape and uniform size. Meanwhile, in the hyperoxia group, as age increased, the number of alveolar was reduced, the small blood vessels expanded, the alveolar hemorrhage was increased, the interstitial cells were increased and the lung tissue was swelling. The levels of SP-C, SP-D decreased with the increase of age in the air group. The level of SP-C in hyperoxia group was lower than that in the air group on the first day. It was higher than that in the air group on the third day, peaked on the seventh day, and then it began to decline on the tenth day and decreased more obviously on the fourteenth day. The level of SP-D in hyperoxia group was not significantly different from that in the air group on the first day, was higher than that in the air group on the third day and peaked on the seventh day. Then it began to decline on the tenth day and decreased more on the fourteenth day. Conclusions　Long-term inhalation of high concentrations of oxygen inhibits alveolar development. With the prolonged time of oxygen inhalation, the apoptosis of lung epithelial cells is increased, and the level of SP-C and SP-D in BALF was increased first and then decreased.