Objective. While topical therapies are common in wound care, the objective of this study was to evaluate the effect of combination topical therapy. Material and Methods. The authors designed a device that could irrigate and apply topical oxygen and topical negative pressure on the wound. A round full-thickness excision wound was made on the backs of 30 rabbits, and the animals were randomly divided into 2 equal groups. The rabbits in the treated group received cycles of irrigation, negative pressure, and topical oxygen therapy 3 times a day for 60 minutes. In the control group, the wounds were irrigated with normal saline. The wound area was determined by image analysis software on days 1, 3, 7, 14, and 21 after the initial wound creation. The Mann-Whitney U test was used to analyze the data with SPSS 16.0 software. Results. On day 3 after wound creation, the percentage of wound closure in the treated group and control group was 30.1% and 3%, respectively, which shows the significant difference in healing (P = 0.0001). This trend was preserved in the rest of the study. Histological studies showed obvious enhancement in wound healing in the intervention group. Conclusion. The combination of the topical methods might have synergistic effects on wound healing.