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Background: Researchers have mentioned many beneficial effects for the compounds present in the toothbrush tree (Miswak) (Salvadora persica: SP); such as anti-inflammatory, antioxidant and antimicrobial activities. The current 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. The mice were divided into 5 groups of twelve. Groups 1 and 2 were respectively treated with concentrations of 5% and 10% of aqueous-alcoholic extract of the toothbrush plant, group3 was treated with silver sulfadiazine ointment (positive control), group4 was treated with Vaseline (negative control), and group 5 (sham) received no treatment. A second-degree circular burn wound with a diameter of 1 cm was made on the back of the animal. The first to fourth groups were dressed twice a day. On days 4, 7, 10 and 14, sampling was performed from the wounded site and wound healing was evaluated histopathologically. Results: Inflammation and infiltration of neutrophils and lymphocytes, being compared to the negative and sham control groups, were significantly reduced in the group treated with 10% SP extract (P