Aim:Complicity and slow rate of axons regeneration necessitates microsurgery that adjuvant therapy can help it. Improving nerve metabolic capacity and response to neural growth factors are positive effects of simvastatin and L-carnitine. To decrease neuronal loss after axotomy and improve neuronal regeneration, this study was designed to assay effects of these agents on nerve repair.Material and Methods:Left sciatic nerve of 70 female rats were cut and repaired under aseptic microsurgery. Based on medications and treatment period, seven groups were formed. Control: no medication. SIM1W: one week daily oral simvastatin. LC1W: one week daily oral L-carnitine. Plb1W: one week daily oral placebo. SIM1M: one month daily oral simvastatin. LC1M: one month daily oral L-carnitine. Plb1M: one month daily oral placebo. Following 90 days, behavioral assessments and then histopathology were done.Results:Mean reflex time of withdrawal reflex latency and toe out angle in all experimented groups increased than normal. Long-term drug-medication significantly improved toe out angle. In long-term drug-medication, inflammation and neural bundle differentiation were significantly lower and higher, respectively. Vascular index showed reduction but number of myelinated nerve fibers had rises in drug-medicated groups compared to control and placebo groups. No obvious differences were detected in myeline diameter.Conclusion:Both Simvastatin and L-carnitine can accelerate and improve the process of nerve regeneration in a long enough treatment period. The regulatory influence of these exogenous neurotrophic drugs may be essential to optimize regeneration of nerve fibers; so can broaden horizons for novel therapeutic modalities to decrease neuronal apoptosis.