Abstract: Objective To investigate the changes of lung cell apoptosis and the expression of notch signaling in the lung of neonatal rats exposed to hyperoxia and to explore the internal relationship between notch1 and hyperoxia-induced lung injury. Methods 120 neonatal Sprague-Dawley rats of 22-day gestational age were randomized continually exposed to hyperoxia (FiO2=95%, hyperoxia group) or room air (FiO2=21%, air group) 30 minutes after birth. The notch signaling expression in the lung were detected by immunohistochemical methods respectively at 4, 7, 14 days after inhale hyperoxia or air. At the same time, pathological changes in the different groups were also observed with light microscope and lung cell apoptosis was determined quantitatively by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) methods. Results The biopsy test showed lung injury in hyperoxia group. The amount of apoptosis cell in hyperoxia was higer than that in the control group, and increased with the prolongation of hyperoxia supply. Positive staining for North1 in hyperoxia group was much lower than that in control group at every time point (P<0.01, P<0.05). Conclusion Continually hyperoxic exposure might resulted in the lung injury and development of arrest. The abnormal expression of notch signaling might contributed to the pathogenesis of hyperoxia-induced lung injury in newborn rats.