Purpose: Radioactive I131 (RAI) therapy is a standard method to ablate the remnant thyroidal tissue after total thyroidectomy and its metastases in differentiated thyroid carcinomas; however, I131 also accumulates in nonthyroidal tissue, which may cause adverse effects and limit the I131 dose required for treatment. We hypothesized that montelukast, a known agent with anti-inflammatory and anti-oxidant properties, would ameliorate the radiation-induced histopathological characteristics such as pneumonitis and fibrosis in rat lungs after RAI.Methods: Fifty female Wistar albino rats were randomly separated into five groups of 10. Group 1 was the control group; Group 2 was administered RAI only; Group 3 was administered RAI and montelukast, Group 4 was administered RAI after total thyroidectomy and Group 5 was administered RAI and montelukast after total thyroidectomy. All rats were sacrificed after 12 weeks and the lungs were evaluated in the histological examination to determine the degree of inflammation and fibrosis and for immunohistochemical (IHC) staining for tissue expression of IL-1, IL-6 and TNF-alpha and TGF-beta.Results: The RAI-administered groups, Group 2 and Group 4, were significantly different from the control group, however, the groups medicated with both RAI and montelukast, Group 3 and Group 5, were not significantly different from the control group. All histopathological and IHC parameters were significantly less in the groups administered with montelukast compared to the groups not administered with montelukast.Conclusions: The results of this study demonstrated the radioprotective effect of montelukast in the pulmonary system through histopathological and IHC examination.