Tissue expansion has been widely used to provide additional soft tissue for clinical reconstruction. Rapid expansion requires a much shorter clinical period than conventional expansion; however, less natural skin growth occurs resulting in a larger stretch-back ratio and insufficient extra soft tissue for clinical use. In this study, hyperbaric oxygen therapy (HBOT) was used in the inflation phase of rapid expansion to increase natural skin growth. Twelve rabbits were divided into two groups. Each group received rapid expander inflation every day. One group received HBOT and the other did not. Blood flow in the expanded skin of each rabbit was assayed in the 10-day inflation phase. After the inflation phase, a rectangular expanded flap of each rabbit was harvested. The instant stretch-back ratio, tension, weight and histological characteristics of the flaps were evaluated. (1) After the second inflation day, the mean blood flow of the HBOT group became significantly higher than that of the control with each day (P < 0.05). At the last day, the blood flow of the HBOT group increased to 131 ± 17 pu, while the control group decreased to 35 ± 5 pu. (2) The mean instant stretch-back ratio of the HBOT group under no-tension conditions was 29 ± 4%, which was significantly less than that of the control group, 46 ± 3% (P < 0.01). (3) The mean flap tension of the HBOT group was 15.3000 ± 1.47648 g and 12.9833 ± 0.73598 g in the transverse and longitudinal axis, respectively, both significantly smaller than that of the control group (33.9167 ± 4.78390 g and 26.5000 ± 2.45031 g, respectively) (P < 0.01). (4) Mean per unit flap weight of the HBOT group was 0.221 ± 0.005 g cm(-2), significantly heavier (P < 0.01) than that of the control group (0.143 ± 0.010 g cm(-2)). (5) Histologically, the epidermal layer and thickness of the expanded skin of the HBOT group were much thicker than those of the control group, and more vessels were visible in the subcutaneous tissue. The use of HBOT in the inflation phase of rapid expansion can effectively promote blood flow in the expanded skin, increase its natural skin growth and reduce the instant stretch-back ratio and tension of expanded skin. Ju, Wei, Guan, Zhang, Liu, Feng, , , (2012). Effects of hyperbaric oxygen therapy on rapid tissue expansion in rabbits. Journal of plastic, reconstructive & aesthetic surgery : JPRAS, 2012 Sep;65(9):1252-8. https://www.ncbi.nlm.nih.gov/pubmed/22512939