This study was conducted on 20 rabbits were divided into control and treated groups (8 and 16 weeks) for each groups. Animals were anesthetized then left sciatic nerves were compressed for 30 seconds with artery forceps. Zinc oxide nanoparticles have been used in treated groups 56 days of daily monitoring. Improved gait and absent knuckling were observed  at days 20 and 28 post-operatively. Muscle was strong contraction and modest atrophy during day 56 PO, while the treated group's animals displayed notable sensory responses (p ≤0.05). In the treated group the highest ratio of relative gastrocnemius muscle weight measurement )RGMWM( were (0.74) and (0.71) at weeks 16th and 8th, respectively, and (0.54) in the control group on day 112 PO. On day 56 PO, there was a no significant decrease in RGMW values in the control group at 16 and 8 ws (30 and 25)% respectively and 25% in the treated group. The conductive velocity at 8 weeks PO showed non-significant differences between all groups, the latency value of the treated group was 3 ms and  4 ms in the left and right limb, respectively, and amplitude values in the left and right limbs in each treated and control groups were (3.5 and 6.9) Mv and (2.83 and 5.2 ) Mv respectively. In the treated group histopathological examinations showed advantage in quality and quantity of nerve fibrous formatting in a period of 16 weeks PO. We witnessed that ZnO-NP were a vital and essential for enhancing nerve regeneration.