Purpose: To evaluate the effect of histone deacetylase (HDAC) inhibitor, trichostatin A (TCA), on cartilage regeneration in a rabbit perichondrial graft model. Methods: Perichondrial grafts (20 x 20 mm2) were derived from the ears of New Zealand rabbits and transplanted onto the paravertebral muscle of the face of each rabbit. The rabbits were separated into three groups: non-treated control group, vehicle-treated control group that received 0.3 mL of saline, and TCA-treated group administered 0.3 mL of TCA (500 ng/mL). Rabbits in all three groups were further divided into subgroups according to the duration of treatment after transplantation: 2, 4, 6, and 8 weeks (n = 12 rabbits each). The effect of TCA on cartilage regeneration was determined histologically by evaluating the thickness of the cartilage plate in the grafted rabbits. Results: TCA increased the amount of immature cartilage 4 and 6 weeks after perichondrial graft implantation. Mature cartilage was seen in the TCA-treated rabbits 8 weeks after transplantation. The thickness of the cartilage plate was significantly (p < 0.01) higher in TCA group (905 +/- 36) than in either the non-treated (632 +/- 22) or the vehicle-treated control (639 +/- 22) group. Conclusion: Treatment with trichostatin A, an HDAC inhibitor, enhances cartilage regeneration in rabbit recipients of a perichondrial graft. Furthermore, the findings of this study should be helpful in exploring the clinical use of trichostatin A.