Abstract: Objective To observe the effect of nuclear factor erythroid 2-related factor 2 （Nrf2） agonist on the apoptosis of alveolar cell induced by hyperoxia and to explore whether Nrf2 activation could protect neonatal rats from hyperoxia induced lung injury. Methods 90 neonatal Sprague-Dawley rats were randomized into room air group (FiO₂ =21%, N group), hyperoxia group (O group) and Nrf2 group (n=30 each).Neonatal rats in the O group and Nrf2 group received saline 0.2 mL and Nrf2 agonist 30 mg/kg respectively at the first and second day after birth, and were exposed in high concentration oxygen (95%) for 4 d. N group rats were fed in room air. The apoptotic index (AI)and Nrf2 expression of lung tissue were detected by TUNEL and immunohistochemistry staining respectively. Results Compared with O group (28.8%±3.0%), the AI of alveolar cell was lower in N group (0.7%±0.6%) and Nrf2 group (7.2%±0.8%)（P<0.01）. The expression of Nrf2 was significantly higher in O group (926.80±130.51) and Nrf2 group (1 038.40±151.12) than that in N group (30.03±9.99)（P<0.01）. Conclusion Nrf2 activation could reduce the alveolar cellular apoptosis and protect neonatal rats from hyperoxia induced lung injury.