Psychological stress has been shown to dysregulate healing in both humans and animals. Studies indicate the possibility for decreased oxygen supply, and increased oxygen demand, in the wounds of the stressed animals. Oxygen is an important mediator of wound healing, and its availability can limit healing rate. Hence, in a mouse model of stress-impaired healing, the hypothesis that hyperbaric oxygen therapy would ameliorate the effect of stress on dermal wound healing was tested. Hyperbaric oxygen therapy (HBO) twice a day during early wound healing significantly ameliorated the effects of stress, bringing healing to near-control levels. There was no significant effect of HBO on the wounds of control animals. Wound inducible nitric oxide synthase (iNOS), modulated by psychological stress and oxygen balance, was studied for gene expression by real-time PCR. Expression of iNOS increased in stressed mice on days 1 (205%; p<.0001), 3 (96%; p<.03), and 5 (249%; p<.03), post-wounding. HBO treatment of the stressed animals decreased iNOS expression by 62.6% (p< .02) day 1 post-wounding. There was no significant effect of HBO on wound healing and iNOS expression in the control animals. Methods aimed at increasing tissue oxygenation, like HBO, have a high therapeutic potential. Their molecular mechanisms, implicated in wound healing, elude clarification due to the lack of appropriate animal models. Our current findings represent the first experimental evidence, demonstrating that HBO corrects stress-impaired dermal wound healing.