BACKGROUND: Peripheral nerve injuries are one of the most common and costly injuries especially in the young population. In this study, it is aimed to determine the histological role of epidermal growth factor (EGF) in nerve regeneration with an acute damage made on sciatic nerve in the rabbit model. METHODS: We used 18 New Zealand rabbits (nine in control group and nine in experimental group). Each group was divided into two groups consisting of five rabbits planned for diameter measurement and four rabbits planned for spatial measurement. The sciatic nerve exploration in the right flank of each animal, full-thickness nerve damage, and then epineural repair was made by a single researcher. 10 μg/kg EGF was given to the repair area of the experimental group and five more EGF injections were given to the experimental group every other day postoperatively. In the control group, we used saline solution. Rabbits were observed for 8 weeks. During follow-up, two rabbits died. At the end of 8 weeks, the nerve tissue of each animal was evaluated histologically and morphologically. RESULTS: In the experimental group consisting of five rabbits, the mean thickness of connective tissue (epineurium+ mesoneurium) was 156,867 μm; while, in the control group, the thickness was 25,170 μm. In the other groups, the numerical increase in epineurium and mesoneurium areas was detected in the EGF (+) group as a result of the comparative spatial measurements. Epineurium and mesoneurium enlargement was observed in the EGF-given group. Adipocyte and capillary increase was observed in connective tissue. CONCLUSION: EGF increases epineurium and mesoneurium diameters in peripheral connective tissue in acute peripheral nerve injury regeneration. However, further studies are needed to understand this effect clinically and physiologically.