Abstract: Objective To investigate the effect of continuous exposure to hyperoxia on livers and changes in nuclear factor erythroid 2-related factor 2 (Nrf2) expression in hepatic tissues in neonatal rats. Methods 100 neonatal Sprague-Dawley rats were randomized divided into hyperoxia group (FiO2=95%, O group) and normal control group (FiO2=21%, N group) immediately after birth. Hepatic apoptotic index and Nrf2 expression were detected by immunohistochemical methods on 4 d, 7 d, and 14 d. Results Rats with hyperoxia had higher levels of hepatic apoptotic index and Nrf2 expression compared with the controls (P<0.01). The levels of hepatic apoptotic index and Nrf2 expression in rats with hyperoxia were higher on 7 d and 14 d than those on 4 d (P<0.01). Conclusion Continuous exposure to hyperoxia could result in hepatic damage to neonatal rats, with increased expression of Nrf2 as a mechanism of anti-oxidant.