Objectives In this study, pirfenidone's role about reducing tracheal stenosis by suppressing fibrosis and inflammation was examined. Methods Tracheotomy was performed on 14 rats, and their cannulas were fixed to tracheotomy area by stoma suture. Two working groups were established. Rats in the first group were given 15 mg/kg/day (1 mL pirfenidone solution) pirfenidone intraperitoneally for 10 days. In the second group as a control group, 1 mL saline solution was applied intraperitoneally. Ten days later, rats were decanulated and kept alive for 3 more weeks. Anesthetized rats were sacrificed on day 30. All rat tracheas were resected between the first and seventh rings. Epithelial damage, inflammation, and fibrosis were determined histopathologically; diameters of intratracheal lumen and their mucosal thickness parameters were determined histomorphometrically; and TGFβ‐1 (the growth factor beta), TNFα (tumor necrosis factor alpha), and IL‐1β (Interleukin‐1 beta) values were determined immunohistochemically. Results According to the parameters of the control group, fibrosis; diameters of intratracheal lumen; and values of TGFβ‐1, TNFα, and IL‐1β were found to be statistically significant. Conclusion In our study, it was found that pirfenidone reduces fibrosis and narrowing of intratracheal lumen diameter significantly. Level of Evidence NA Laryngoscope, 129:E178–E186, 2019