OBJECTIVE: To investigate the function of BDH2 in an in vivo or in vitro model of idiopathic pulmonary fibrosis (IPF). STUDY DESIGN: Fifteen C57BL/6J mice were divided into control group, IPF model group, and anti-BDH2 group. IPF model mice were administered intratracheally with 3 U/kg bleomycin. Anti-BDH2 group, IPF mice were administered intratracheally with anti-BDH2 body (1 μg/mice). In vitro, human idiopathic pulmonary fibrosis cells were transfected with BDH2, NRF2, siBDH2, siNRF2, or microRNA mimics. ROS production was measured by ELISA. The expressions of BDH2 and NRF2 were tested by RT-PCR and western blot. RESULTS: The expressions of BDH2 mRNA and protein in the lung tissue of IPF mice were increased. BDH2 inhibition prevented pulmonary fibrosis in mice with IPF. BDH2 promoted oxidative stress in the in vitro model of IPF, and siBDH2 reduced oxidative stress in an in vitro model of IPF. The inhibition of NRF2 reduced the effects of anti-BDH2 on oxidative stress in the in vitro model of IPF. The activation of NRF2 reduced the effects of BDH2 on oxidative stress in the in vitro model of IPF. CONCLUSION: Our results demonstrated that BDH2 inhibition prevented pulmonary fibrosis through anti-oxidation effects by NRF2 in an in vivo or in vitro model of IPF. © Science Printers and Publishers, Inc.