Purpose: This study was to evaluate the synergistic effects of combined therapy of steroid and anti-neoplastic drug injection on hypertrophic scars in a rabbit model. Methods: Adult male white rabbits weighing about 2.5 kg were used. After full thickness wounding (about 6 mm) over the ventral surface of each ear sized was made, either saline (control group), triamcinolone, 5-fluoruracil, and mixture of triamcinolone and 5-fluoruracil were injected once 16 days after the wound was made. Rabbits were sacrificed 2, 4 and 8 weeks after injection, and tissue specimens were prepared for histologic and histomorphometric examinations. Results: With the combined injection of triamcinolone and 5-fluoruracil, collagen fiber thickness was arranged in a somewhat irregular manner 2 weeks after injection. After 4 weeks, blood vessels and inflammatory cells were decreased, and collagen fibers were arranged in an almost parallel manner. By 8 weeks, almost same amount of connective tissue compared with adjacent normal tissue was observed. Conclusion: These results indicated that combined injection of triamcinolone and 5-fluoruracil reduced the amount of hypertrophic scars by inhibition of fibroblasts and inflammatory cells. Therefore, combined injection of triamcinolone and 5-fluoruracil is a more potent and effective treatment of hypertrophic scars compared with the single injection of either triamcinolone or 5-fluorouracil.