Introduction: Despite its potentially pulmonary complications, Methotrexate (MTX) is widely utilized in the treatment of arthritis. Several studies reported development of various forms of lung disease in patients treated with MTX. The aim of this study is to investigate the adverse effects of MTX on the lung structure and the likelihood of recovery following MTX withdrawal. Materials and Methods: A total of 30 albino rats were studied in 3 different groups of ten rats. Group I was considered as control whereas group II (MTX treated group), received 5 mg/ kg subcutaneous MTX (SC) for 5 days. Lastly, group III (withdrawal group) received similar doses of MTX for the same duration but sacrificed 5 days after MTX withdrawal for lung dissection and histological examination. Results: The lungs of MTX treated rats demonstrated a significant increase in the inter-alveolar thickness with concomitant mononuclear cell infiltration linked with alveolar collapse and damage. After MTX withdrawal, the changes in pulmonary structure exhibited partial recovery. This in turns suggests that MTX-induced lung toxicity was to some extent reversible. Conclusion: MTX could result in pulmonary inflammation and alveoli damages, therefore, this study recommends regular examinations for MTX patients designed for early detection of interstitial pneumonitis.