Introduction: Obstructive sleep apnea (OSA) is highly common among patients with idiopathic pulmonary fibrosis. OSA causes chronic intermittent hypoxia (CIH) during sleep. We aimed to investigate the effect of CIH on bleomycin-induced pulmonary fibrosis in mice and to explore putative mechanisms. Methods: C57/BL6 mice were divided into four groups and then exposed to control conditions (room air) or CIH for 2 weeks prior to the intratracheal injection of bleomycin. After bleomycin instillation, mice were exposed to CIH or room air for 4 weeks. Fibrosis was evaluated by Masson’s trichrome stain and hydroxyproline assay. The mRNA expressions or protein levels of fibrosis-related genes were measured by real-time PCR and western blot in lung tissue, respectively. Results: Masson staining showed that CIH led to scattered fibrotic changes in alveolar structure and substantive fibrotic tissue dominantly situated in the perivascular space. In bleomycin-treated group, CIH compared to control increased hydroxyproline (p＜0.001) in lung tissue and TGF-β (p＜0.01) in serum. CIH increased the mRNA expression of TGF-β, collagen 1, and α-SMA in bleomycin-treated group, though the difference was not statistically significant. The protein levels of TGF-β1, collagen 1, and p-Smad2/3 were elevated in CIH with bleomycin-treated group. The protein level of snail was notably increased in CIH, regardless of bleomycin treatment. Conclusion: Following bleomycin-induced lung injury, CIH might exacerbate the progression of pulmonary fibrosis via TGF- β/Smad/Snail signaling.