Background: Wound healing has a vital importance for the organism and various agents are used to accelerate wound healing. Although the effect of boron on wound healing is known, its mechanisms are not completely clear yet. In this study, the effect of boron in the Ephrin /Eph pathway will be evaluated. Methods: Forty adult female rats were used in the study. A full-thickness excisional wound model was created in all groups divided as Control, Fito, Boron and Plu groups. After the applications performed twice a day and lasting 7 days, skin tissues obtained and evaluated histopathological (inflammatory cell infiltration, oedema, and fibroblast proliferation density) and immunohistochemical (TNF-α, EphrinA1, EphrinB1, EphrinB2 and EphB4). Results: Inflammatory cell infiltration score was found to be higher in the Fito group compared to Boron group (p =.018). Fibroblast proliferation density was higher in Plu group than Boron group (p =.012). While TNF-α was lower in boron group than Plu (p =.027) and Fito (p =.016) groups, EphrinA1 was higher in Boron group than Plu group (p =.005). EphrinB1 expression was higher in Boron group compared to Plu (p =.015) and Fito (p =.015) groups, and the same difference was also observed in EphrinB2 (p values.000). Similarly, EphB4 immunoreactivity was higher in the Boron group compared to Plu (p =.000) and Fito (p =.002). Conclusion: One of the mechanisms of action of boron in wound healing is to increase EphrinB1, EphrinB2 and EphB4. Low TNF-α and histopathological findings indicate that boron limits extensive wound healing.