Background and aims: Wound healing is one of the most important issues in medical science. Synthetic drugs have long been introduced and used to speed up the healing process of wounds, but most of them have many side effects. The present study was performed to evaluate the healing efficiency of watercress seed mucilage (Lepidium sativum L.) on wounds. Methods: In this study, the animals were randomly divided into five groups. The treatment groups were (1), (2), (3), sham (4), and control (5). The treatment groups were treated with 20%, 10%, and 5% watercress seed mucilage in the Eucerin base, respectively, and the sham was treated with Eucerin, while the control received no treatment. Then, 5 pairs of full-thickness wounds with a diameter of 7 mm were created on both sides of the rabbit’s spine. Macroscopic and wound area studies were performed on days 4, 7, and 14 after surgery. Results: According to the analysis of variance, there was a significant difference between groups 1, 2, 3, sham, and control (P=0.001), but no significant difference was observed between group 3, sham group, and control group (P=0.993). Based on these findings, at the end of the treatment period, group 1 had the highest healing rate and the lowest wound area (1.12±0.77) compared to group 2 (4.42±0.30) and 3 (7.05±0.35), as well as the sham (8.34±1.10) and control (8.50±1.90) groups. Thus, the treatment method of this group has been more effective in wound healing than that of the other treatment groups. Conclusion: It seems that watercress seed mucilage can treat wounds due to its important compounds such as flavonoids, phenols, and vitamins A and C.