OBJECTIVE: To explore the temporal expression of tumor necrosis factor-α(TNF-α) and Caspase-3 in hyperoxia-induced lung injury in preterm rats. METHODS: Two-day-old Sprague-Dawley preterm rats were randomly divided into Air group and Hyperoxia group (both n=40). Rats in the Hyperoxia group were exposed to 85% O_2, while rats in the Air group were exposed to air. The rats in each group were sacrificed at 1, 4, 7, 14 and 21 days after exposure (8 rats at each time point), and lung tissues were collected. Pathomorphology of the lungs was observed by hematoxylin-eosin staining. The contents of TNF-α in the homogenate of lungs were detected using ELISA. The expression of Caspase-3 was detected by immunohistochemistry and Western blot. RESULTS: The contents of TNF-α in the homogenate of lungs increased significantly at 4, 7 and 14 days after exposure, and the expressions of Caspase-3 were also enhanced, as compared with those of the Air group(P<0.01). The expression of Caspase-3 positively correlated with the contents of TNF-α (r=0.93,P<0.01). CONCLUSIONS: Over-expression of Caspase-3 induced by TNF-α might be one of the underlying mechanisms of hyperoxia-induced lung injury in preterm rats