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Background: There have been clinical observations indicating that wound healing could be affected in patients undergoing systemic isotretinoin treatment. However, the precise role of retinoids in wound healing is still unclear and controversial. It is generally assumed that systemic retinoids could be harmful to wound healing, but this requires further investigation., Methods: Sprague-Dawley rats were gavaged with 2 mg/Kg/day of Isotretinoin and divided into three groups: Control, Isotretinoin/1month and Isotretinoin/2month. Photographic documentation and histomorphometric investigation were performed. The mRNA expressions of IL-6, MCP-1, VEGF, ICAM1, L-Selectin, TGF-1β, IL-10, IL-1α, and IL-8 were examined by qRT-PCR., Results: There was no significant impact on the rate of wound closure in Isotretinoin/1month group. However, a two-month regimen accelerated the wound-healing process. RT-PCR results revealed increased expression of IL-6, IL-8, IL-1α, TGF-β1, IL-10 MCP-1, ICAM1, L-Selectin, and VEGF rats that were administered Isotretinoin. Histological observations showed an increased number of mast cells in the wound areas of rats treated with Isotretinoin., Conclusion: Our research indicated that taking Isotretinoin did not slow down wound healing and may even help the growth phase. Additionally, we did not observe any keloid formation during our histopathological analysis, suggesting that it may not be necessary to postpone invasive surgical procedures for six months after Isotretinoin therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)