Background: Perfluorooctanoic acid (PFOA) is an environmental persistent agent to which humans are exposed daily through food and water. Research design and methods: This study investigated the lung toxic effects induced by ingested PFOA (30mg/kg/day) for 8 weeks in adult male rats and the impact following 8 weeks of its withdrawal. Results: PFOA increased MDA and reduced TAC inducing oxidative stress. It induced airway hyperresponsiveness (AHR)via increased bronchoalveolar lavage fluid (BALF) IL-4, IL-5, IL-13, IL-9, eosinophil count, TNF-α and IL-1ß, and reduced IL-12, increased serum IgE, and increased urocortin expression in lung tissues. Moreover, it induced pulmonary fibrosis via increased serum KL-6, and SFTP-D, altered pulmonary structure, and increased deposition of collagen fibers in lung tissues. Furthermore, it increased TGF-β1, Smad2, and Smad3 and reduced Smad7 gene expression in lung tissues. These gene alterations were positively correlated with AHR and fibrosis-related factors. The recovered lung upon PFOA withdrawal showed complete resolution of oxidative stress and slight amelioration of other studying parameters. Conclusion: exposure to PFOA induced lung toxicity by disrupting the TGF-β1/Smad signaling pathway, which acts as a crosstalk between AHR and fibrosis. Additionally, PFOA altered pulmonary architecture, triggered inflammation, and caused oxidative stress. The lung exhibited partial alleviation upon recovery.