This paper aims to investigate the effect of topical application of pentoxifylline and zinc oxide combination on experimental full-thickness wound healing in rats. Forty-eight adult male Wistar rats weighing 250 to 300 g were randomly divided into four groups of 12: Control (C), Zinc oxide (Z), Pentoxifylline (P), and Zinc-Pentoxifylline (ZP). For topical use of pentoxifylline, the ointment was formulated as 5%. All rat were anesthetized by intraperitoneal administration of a combination of xylazine 2% and ketamine 10% and after transfer to the operating table, under aseptic conditions, using a sterile ruler and surgical razor, a 2×2 cm2 skin defect in the back was created. In order to manage the wound, each group received appropriate treatment. In the ZP group, the combination of pentoxifylline and zinc oxide was treated in a ratio of 1:1. On days 7, 14, and 21 after facilitation, a subgroup of each main group was sampled, then the samples were examined macroscopically and microscopically. At the end of this period, the highest percentage of the healing, wound closure, and keratinocyte migration and the lowest inflammation belonged to the PZ group. The rate of inflammation and the number of inflammatory cells at the end of the period were lower in the ZP group than Z group and there was a statistically significant difference (p ≤ 0.05). Overall, this study showed that wound healing is performed with better speed and quality following topical application of a combination of zinc oxide and pentoxifylline. However, more studies are needed to confirm this conclusion.