Abstract: Objective To explore the therapeutic effect of oral or topical administration of pirfenidone on hypertrophic scar of rabbits ears. Methods A total of 20 Japanese white rabbits(2.0-2.5 kg) were divided into 4 groups randomly. Animal model of hypertrophic scars was established in group A, group B and group C. Group A were fed with 0.5% pirfenidone powder mixed with food; Group B were treated with 8% pirfenidone ointment topically; Group C served as positive control while group D was the negative control. Two months after the surgery, hypertrophic scars were measured. Hematoxylin and eosin staining and Masson's trichrome staining were also performed. Results The hypertrophic scars of group A were thinner than those of group B and group C. HE and Masson's trichrome staining results also showed collagen reduced in group A. Conclusion Oral administration of pirfenidone had effect on inhibiting hypertrophic scar to some extent, while topical administration does not work signifcantly.