Aim:Peripheral nerve injury (PNI) is a persistent public health problem that frequently leads to significant impairment in motor and sensory functions and to permanent disability. In our research we aim to compare the effects of pregabalin and gabapentin on the regeneration of rat nerves exposed to experimental axonotmesis by means of histomorphological, immunohistochemical, biochemical, electrophysiological, and clinical evaluations. Material and Methods:32 female Sprague-Dawley rats were divided into four groups with eight in each. Group 1 (control), group 2 (axonotmesis + normal saline), group 3 (axonotmesis + pregabalin 30 mg/kg), group 4 (axonotmesis + gabapentin 30 mg/kg). Medical treatment is given for first seven days to group 3 and 4. Functional recovery was assessed using the electromyography (EMG) and sciatic functional index (SFI). Sciatic nerves were excised for histomorphological, immunofluorescence and immunohistochemically examination. Biomarkers was measured by enzyme-linked immunosorbent assay methodResults:Significant improvement in SFI scores and EMG measurements on the 28th day was observed in groups 3 and 4 (treated groups), while group 2 (untreated) showed inadequate recovery. Histomorphological and immunohistochemical analysis revealed notable reductions in wallerian degeneration, necrosis, inflammation, and nuclear factor-kappa B (NF-κB) expression levels in the treated groups compared to group 2. Groups receiving medical treatment exhibited increased staining areas for nerve growth factor (NGF). Biochemical assessment indicated elevated levels of NGF, ciliary neurotrophic factor (CNTF), Transforming growth factor beta (TGF-β) and myelin basic protein (MBP) in the treated groups compared to group 2. Conclusion:Overall, our findings suggest that both pregabalin and gabapentin exert neuroprotective effects and contribute to the regeneration process, with no apparent superiority of one over the other