Adapalene is a new naphthoic acid derivative with strong retinoid agonistic pharmacological properties. We propose that adapalene might contribute to the wound repairing process as is detected with retinoids. In this controlled study, the effects of topical adapalene, tretinoin and collagenase on full-thickness wound healing were compared in an animal model. Thirty-two adult male Wistar-Albino rats were used in the study. Two circular, full-thickness wounds were made for each animal with a standard 8-mm punch biopsy, on both sides of the midline on the back. No treatment was given to Group I rats (n:8) which comprised the control group. Tretinoin cream (0.1%) was applied topically in Group II (n:8), adapalene gel (0.1%) in Group III (n:8), and collagenase ointment in Group IV (n:8) once daily. On day 7, the wounds were photographed to measure the wound surface area. The wounds on the left side of each animal were excised on day 7, for histopathologic and biochemical examination. The treatments were continued for the right side wounds up to 14 days when the same procedure was repeated. In Group II, a significant decrease in hydroxylproline (HP) levels was detected at day 7 (p = 0.018), and an increase at day 14 (p = 0.002) compared to the control group. HP results revealed no difference either in Group III nor in Group IV versus control at day 7 or 14. However, findings of improved healing were more prominent in Groups II and III than the other groups in histopathologic examination. In conclusion, tretinoin and adapalene contributed to the wound healing process resulting in an enhancement of collagen production, angiogenesis and granulation tissue formation.