• AIM: To determine the effect of pirfenidone on the activated human Muller cells by platelet-derived growth factor-BB (PDGF-BB). • METHODS: The primary human Muller cells were separated from retinal tissues and established the pathogenic model by stimulated with PDGF-BB. The Muller cells behaviour of normal group and the model group was measured by MTT assay, Trypan blue assay, cell migration assay, and collagen contraction assay. The expression of transforming growth factor (TGF)-β1, -β2, and pigment epithelium-derived factor (PEDF) was estimated with realtime polymerase chain reaction (PCR), Western blot and immunofluorescence analyses. • RESULTS: A pathogenic/proliferative model of Muller cells was established by stimulating normal cultured Muller cells with 10 ng/mL PDGF-BB for 48h. After treated with 0.2 and 0.3 mg/mL pirfenidone, the proliferation, migration and collagen contraction was statistically significantly depressed in the model group compared with the normal groups. The expression levels of TGF-β1 and TGF-β2 were significantly down-regulated, while the PEDF expression was significantly up-regulated after treated with 0.2 and 0.3 mg/mL pirfenidone in the model group. • CONCLUSION: Pirfenidone effectively suppress the proliferation, migration and collagen contraction of the human Muller cells stimulated with PDGF-BB through down- regulation of TGF-β1/TGF-β2 and up-regulation of PEDF. © 2019 International Journal of Ophthalmology (c/o Editorial Office). All rights reserved.