Peripheral nerve injury is a widespread and disabling condition that can impair the individual's daily life. Studies involving medications that may positively affect peripheral nerve regeneration are rare. The aim of this study was to investigate new treatments after peripheral nerve injury using various neuroprotectants, melatonin, alcar and leptin, in the regenerative process in an experimental rat model. Wistar albino rats were randomly divided into eight groups containing equal number of animals. Intraperitoneal injection of melatonin (50 mg/kg, for 21 days), leptin (1 mg/kg, for 21 days) and acetyl-(L)-carnitine (50 mg/kg, for six weeks) was performed postoperatively. Histological and electromyographical assessments of the regenerated nerves were performed 12 weeks after surgery. Stereological analysis was performed to estimate myelinated and unmyelinated axon numbers, surface area, myelin thickness and the myelin thickness/axon diameter ratio for each group. The results showed that only alcar has a beneficial effect on the regeneration of unmyelinated axons. Neither melatonin and leptin nor alcar were observed to have any therapeutic effect on the regeneration of myelinated axons. Alcar therapy has a positive effect on the regeneration of unmyelinated fiber in the sciatic nerve. However, the same effect was not observed in myelinated nerve fibers after intraperitoneal application of melatonin and leptin. (C) 2017 Elsevier B.V. All rights reserved.