Abstract: Objective To investigate the effects of pirfenidone on epidural scar cells after laminectomy and related mechanism. Methods The human epidural scar cells were cultured in vitro. Then, the cells were exposed to different concentrations of pirfenidone. Their viability was measured by CCK-8 assay. Their migration was measured by the wound healing assay. The cell apoptosis was detected by in situ terminal transferase labeling (TUNEL). The levels of transfer growth factor β1 (TGF-β1), α-SMA, collagen type I, Smad2, phospho-Smad2, Smad3 and phospho-Smad3 were measured by Western blot. Results Human epidural scar fibroblasts were successfully isolated and cultured. Pirfenidone decreased the viability of fibroblasts (P<0.05), but did not stimnlate increase the apoptosis of fibroblasts (P>0.05). Pirfenidone inhibited cell migration and the expression of α-SMA, collagen type I, cell proliferation-related proteins and proteins phosphorylation. Conclusions Pirfenidone inhibits the viability and migration of fibroblasts, which may be associated with inhibition of the TGF-β/Smad pathway and myofibroblast transformation.