Background: Researchers have mentioned many beneficial effects for the compounds in the toothbrush tree (Miswak)(Salvadora persica: SP), such as anti-inflammatory, antioxidant and antimicrobial activities. The present study aimed to evaluate the effect of aqueous-alcoholic extract of toothbrush tree on the wound healing of second-degree skin burns in BALB/c mice. Methods: In this study, 60 mature mice (8 weeks) were used. Mice were divided into 5 groups of twelve. Groups 1 and 2 were treated with concentrations of 5% and 10% of the aqueous-alcoholic extract of the toothbrush, respectively, group3 was treated with silver sulfadiazine ointment (positive control), group4 with cream base (negative control), and group5 (sham) received no treatment. A second-degree circular burn wound with a diameter of 1cm was created on the back of the animal. The first to fourth groups were dressed twice a day. On days 4,7,10 and 14 after anaesthasia, sampling was performed from the wound site and wound healing was evaluated histopathologically. Results: Inflammation and infiltration of neutrophils and lymphocytes were significantly reduced in the group treated with 10%SP extract compared to the negative and sham control groups (P<0.01). On the other hand, the number of fibroblasts, followed by collagen production, epithelialization and the formation of new hair follicles in the wound margins on days10 and14 in the group treated with 10 and 5% SP extracts significantly increased compared to the negative control and sham group (P<0.05). The number of fibroblasts and collagen fiber density in the group treated with 10% SP extract showed a significant increase compared to the 5% extract group and silver sulfadiazine (P<0.05). Conclusion: Our findings showed that using extract of toothbrush accelerates the burn wound healing process. So it can be a suitable, cost-effective substitute for available commercial products.