The aim of this study was to investigate the effect of hyperbaric oxygen (HBO) therapy on healing in an experimental model of a degloving injury of the tails of nicotine-treated rats. Thirty-two male Sprague-Dawley rats were randomized to four groups (n = 8): nicotine (group 1); HBO (group 2); nicotine + HBO (group 3); and control (group 4). The mean length of the necrotic parts of the tails at the degloving injury site was significantly higher in group 1 compared with groups 2, 3, and 4, and was significantly lower in group 2 compared with groups 1, 3, and 4. The mean histopathological stage of ulcers at the degloving injury site was statistically significantly higher (more severe) in group 1 compared with groups 2, 3, and 4, and was statistically significantly lower in group 2 compared with groups 1, 3, and 4. It appears that the negative effects of nicotine on wound healing in degloving injuries are negated by the positive effects of immediate HBO therapy.