Objective：This study aims to investigate the effect of bardoxolone methyl （CDDO-Me） on the hypoxia-induced activation of human pulmonary artery adventitia fibroblasts（PAAF）and potential mechanism. Methods：Human PAAF were cultured in vitro and randomly divided into four groups：the normoxia group（21% oxygen），the hypoxia group（1% oxygen），the hypoxia plus CDDO-Me group and the normoxia plus CDDO-Me group. Cell viability was determined by CCK-8 assay. Transwell assay was carried out to assess cell migration. The levels of reactive oxygen species（ROS），malondialdehyde（MDA），glutathione（GSH）and superoxide dismutase（SOD）were detected to evaluate the level of oxidative stress. The levels of transforming growth factor（TGF）-β1，tumor necrosis factor（TNF）-α and interleukin（IL）-1β were detected by ELISA assay. The expression of α-smooth muscle actin （α-SMA） and nuclear translocation of NF-κB（p65） were detected by immunofluorescence assay. The protein levels of α-SMA，collagen Ⅰ，vimentin，phospho-Smad3 and Smad3，phospho-p65 and p65 were determined by Western blot. Results：CDDO-Me treatment（62.5，125.0，250.0，500.0 nmol/L）decreased hypoxia-induced elevations of cell viability in a concentration dependent manner，which showed significant inhibition at concentration of 250.0 nmol/L and 500.0 nmol/L. CDDO-Me（500.0 nmol/L）remarkably inhibited hypoxia-induced migration and myofibroblast transformation of PAAF，which reflected in improvement of hypertrophy，decreases in expressions of α-SMA，collagenI and vimentin. In addition，CDDO-Me（500.0 nmol/L）significantly inhibited hypoxia-induced increased levels of ROS and MDA，decreased levels of GSH and SOD，and improved the ability of antioxidation. Hypoxia increased the secretion of TGF-β1 and activate TGF-β1/Smad3 signaling pathway in PAAF，which was attenuated by CDDO-Me（500.0 nmol/L）. Besides，hypoxia-induced nuclear translocation of p65，phosphorylation of p65 protein，and the secretion of TNFα and IL-1β were inhibited by CDDO-Me treatment. Conclusion：CDDO-Me can inhibit hypoxia-induced proliferation，migration，myofibroblast transformation of PAAF，improve the antioxidation ability，and inhibit TGF-β1/Smad3 and NF-κB signaling pathway in PAAF.