Objectives: Bronchopulmonary dysplasia (BPD) is a significant global health problem and currently lacks effective therapy. We established a neonatal rat model of BPD to investigate therapeutic potential of bone marrow-derived mesenchymal stem cells (BMSCs) in neonatal hyperoxic lung injury.Methods: BMSCs were isolated, identified, and transfected by lentiviral vector carrying green fluorescent protein gene in vitro. Neonatal Sprague-Dawley rats were injected intravenously with either BMSCs or phosphate-buffered saline following 95% oxygen exposure, and assessed for the survival rate and alveolar injury during recovery.Results: Treatment with BMSCs after oxygen exposure for 7 days improved survival of neonatal rat during recovery. BMSCs protected against neonatal rat hyperoxic lung injury during recovery as demonstrated by enhanced expression of AQP5 and SP-C, likely due to the suppression of alveolar cell apoptosis and lung inflammation responses to oxygen with up-regulation of the expression of BCL-2 gene and down-regulation of the expression of BAX gene and stimulation of vascular endothelial growth factor and so on.Conclusions:BMSCs protect against O2-mediated injury partially through stimulation of potent mediators that participate in tissue repair.