Background: Wound infection has become a major medical problem in recent years. This is usually caused by Gram-positive bacteria, especially Staphylococcus aureus. Since antimicrobial resistance to current drugs has critically been developed in these causative microorganisms, substitution medicine has become one of the main interests within  researchers. OBJECTIVES: The aim of this study was to evaluate the healing activity of Origanum vulgare against surgical wounds infected by S. aureus. METHODS: Twenty male Sprague-Dawley rats were randomly divided into two groups. Excisions were created surgically on the animals’ skin and then infected with S. aureus. Group 1 was treated with an extract of O. vulgare while Group 2 was untreated. Wound biopsy specimens were collected on Days 5, 10 and 16 and analyzed. RESULTS: Results showed that the hydroxyproline content in the treatment group was significantly higher in various post wounding days. The mean of hexosamine in the treated group was higher than in the control group. Protein content increased gradually in Day 10. Results of histopathological studies showed moderate to intense granulation tissue formation and neovascularization in the treated group on Day 10. Furthermore, the histopathological studies showed that intense matrix formation and collagen fiber deposition occurred in treatment group on Day 16 post wound, while intense granulation tissue formation was the prominent feature in control group. CONCLUSIONS: The present study has demonstrated that the ethanol extract of O. vulgare contains properties that accelerate wound healing activities compared to control group.