AbstractThe combination of hyaluronic acid and iodine (Hyodine) has sparked interest in wound care and could have valuable applications in treating burn injuries. We aimed to provide valuable insight into the potential advantages, limitations, and implications of using Hyodine in burn wound management. We studied 25 male rats to assess the clinical outcomes and wound‐healing effects of Hyodine. Each rat received a deep second‐degree burn wound on their back using metal stamps. Subsequently, the rats were then randomly split into two groups. The first group was treated with a layer of Hyodine gel, while the second group received Vaseline. The burn sites were photographed on days 1, 7, 14, and 21 using a digital camera. After excision of the burn wounds, histopathology slides were stained and evaluated in terms of the degree of epithelialization, angiogenesis, inflammatory cells' infiltration, and collagen amount and arrangement. Despite a non‐significant difference regarding the extent of burn wound area between intervention and control groups in the first day of experiment, the rats that were treated with Vaseline showed a significant decrease compared to those who received Hyodine in the second and third weeks (p = 0.02). On the other hand, epithelialization, pathology score, and collagen synthesis were significantly different between days 7, 14, and 21 of each group. However, collagen arrangement and neovascularization were only significantly different between days 7, 14, and 21 in Hyodine group (p = 0.02 and p = 0.03, respectively). The Hyodine gel may offer beneficial outcomes in patients with a burn wound. Based on our findings, despite a non‐significant difference in the extent of burn wound area, using Hyodine revealed a significant improvement in different histopathological variables including neovascularization, and collagen arrangement.