Objective To investigate the effect of 5‐fluorouracil on hypertrophic scar in rabbit ears .Methods The hyper‐trophic scar models in rabbit ears were reproduced and randomly divided into 3 groups (group A ,group B and group C) .On postop‐erative 60th days ,Hematoxylin‐eosin and Masson staining staining was applied to observe themorphological and collagen change of scars under light microscope .Real‐time PCR and ELISA were conducted to detect the expression of TGF‐β,PDGF ,bFGF and INF‐γ .Results HE and Masson staining showed that thinner dermis ,fewer fibroblasts and collagen fibers ,collagen fibers arranged reg‐ularly and less collagen nodule was observed group B compared with the group A and group C .Furthermore ,we found that TGF‐β, PDGF ,bFGF ,INF‐γmRNA and protein expression levels were significantly lower in group B and group C than the group A ,and group B was more effective than group C .Conclusion 5‐fluorouracil is effective for the treatment of hypertrophic scars ,and the lo‐calized injection of 5‐fluorouracil is more effective than the ointment group .