The aim of the present study was to investigate the effect of pirfenidone on bleomycin‑induced lung fibrosis in rats, in order to elucidate the underlying mechanism of periostin‑induced fibrosis. The lung fibrosis model was constructed using a single intratracheal instillation of bleomycin in rats. The normal rats without bleomycin administration were used as controls (n= 24). Bleomycin‑treated rats were randomized into the model (M) or pirfenidone (P) group (n= 24 per group). Rats were sacrificed on days 7, 14 and 28 following treatment. Hematoxylin‑eosin and Masson's trichrome staining were performed to analyze pulmonary alveolitis and fibrosis. Periostin location was detected by immunohistochemistry. Hydroxyproline content, and expression of periostin and transforming growth factor (TGF)‑β1 were detected by ELISA, reverse transcription‑quantitative polymerase chain reaction or western blotting. Correlation of periostin expression with hydroxyproline and TGF‑β1 content was also analyzed. Histological findings demonstrated that pirfenidone significantly inhibited bleomycin‑induced lung fibrosis and reduced the hydroxyproline content on day 14 and day 28 compared with the model group (P< 0.05 or P< 0.01). Furthermore, the bleomycin‑induced increased protein expression of periostin and TGF‑β1 was also significantly suppressed by pirfenidone on days 14 (P< 0.01) and 28 (data not shown). Furthermore, periostin expression was significantly correlated with hydroxyproline and TGF‑β1 content, and fibrosis score (P< 0.001). The present findings suggest that the antifibrotic effect of pirfenidone may be achieved by suppression of periostin and TGF‑β1 expression in rat pulmonary fibrogenesis.