Wound healing is the process of repairing and remodeling damaged tissue. This is a public health problem that can influence the survival rate and quality of life of injured people. This attracts the attention of the medical community because it has high health care costs and there is presently a lack of successful therapy. Thus, the application of natural ingredients and medicinal plants has become a focus of research. The purpose of this study is to investigate the effectiveness of topically-applied sodium usnic acid on macroscopic and microscopic changes under dermal injury. These effects were measured using wound contraction experiments, histological analysis, and immunohistochemistry analysis, and gentamicin was used as a positive control medicine. Our results revealed that wound healing rates were higher and re-epithelialized times were shorter with topical application of sodium usnic acid, as compared to the negative control group. Histological results showed treatment with sodium usnic acid caused a reduction in inflammatory cells and an increase in fibroblast proliferation, granulation tissue, vascular regeneration. Sodium usnic acid treatment also resulted in earlier complete re-epithelialization, formation of well-organized bands of collagen, and epidermal keratinization. Furthermore, the levels of VEGF were significantly higher at day 1 post-wounding in those treated with sodium usnic acid. In conclusion, our results indicate that the topical use of sodium usnic acid could promote skin wound healing, and this mechanism might be related to anti-inflammatory effects at the wound site.