Objectives To investigate the expressions of endoplasmic reticulum stress (ERS)-related factors, glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), in lungs of rats with bronchopulmonary dysplasia (BPD) and their relationship with pneumonocyte apoptosis, and further to explore the role of ERS-induced apoptosis in the pathogen-esis of BPD. Methods A total of 24 neonatal SD rats were randomly divided into control group and BPD group with 12 rats each. Rats in BPD group were exposed to 85%O2, while rats in the control group were exposed to air. Four rats in each group were sacriifced at 7, 14 and 21 days respectively after exposure. The expression of GRP78 in the lung tissues was examined by immunohistochemistry, the mRNA and protein levels of GRP78 and CHOP were detected respectively by real-time PCR and Western blot, and the apoptosis in lung cells were evaluated by TdT-mediated dUTP nick end labeling (TUNEL) assay. Results The mRNA and protein levels of GRP78 and CHOP, and the cell apoptosis in BPD group were signiifcantly different from those in control group (P<0.01) at different time points and increased over the time of hyperoxic exposure (P<0.01). Conclusions En-doplasmic reticulum stress may be initiated by hyperoxic exposure and apoptosis is induced via CHOP signal pathway, which is involved in the pathogenesis of BPD.