Intestinal fibroblasts, the main effector cells of intestinal fibrosis, are 
considered to be a good target for anti‑fibrotic therapy. The aim of the present 
study was to examine the effects of pirfenidone (PFD) on human intestinal 
fibroblasts (HIFs) stimulated by transforming growth factor (TGF)‑β1 and to 
explore the potential mechanism. Prior to stimulation with TGF‑β1 (10 ng/ml), 
HIFs were treated with or without PFD (1 mg/ml). Cell proliferation was 
determined by Cell Counting Kit (CCK)‑8 and colony formation assays, and cell 
apoptosis was assessed using flow cytometry and a TUNEL assay. Reverse 
transcription‑quantitative polymerase chain reaction and western blotting were 
performed to evaluate the mRNA and protein expressions of α‑smooth muscle actin 
(α‑SMA), collagen I and fibronectin. The protein expression of TGF‑β1/mothers 
against decapentaplegic homolog (Smad) and phosphoinositide 3‑kinase 
(PI3K)/protein kinase B (AKT) signaling pathways was evaluated by western 
blotting. CCK‑8 and colony formation assays demonstrated that PFD significantly 
inhibited cell proliferation in HIFs stimulated with TGF‑β1. Flow cytometry and 
TUNEL assays revealed that PFD treatment significantly enhanced apoptosis in 
TGF‑β1‑stimulated HIFs. In addition, PFD markedly reduced TGF‑β1‑induced HIF 
activities, such as myofibroblast differentiation (α‑SMA), and collagen 
production (collagen I and fibronectin). These effects of PFD were mediated by 
the inhibition of the TGF‑β1/Smad and PI3K/AKT signaling pathways. Therefore, 
the present study demonstrated that PFD reduced TGF‑β1‑induced fibrogenic 
activities of HIFs, suggesting that PFD may be a potential therapeutic agent for 
intestinal fibrosis.