Peripheral nerve injury is common and negatively affects an individual's quality of life. Drugs used for peripheral nerve regeneration should aim to eliminate symptoms such as neuropathic pain and have therapeutic effects. In recent studies, pigment epithelium‐derived factor (PEDF) has been considered an essential therapeutic agent because of its potential neuroprotective properties. In this study, we aimed to investigate the efficacy of locally applied PEDF for peripheral nerve regeneration. Twenty‐four Wistar albino male rats were used. The study groups included Injury (n = 12) and Injury+PEDF (n = 12). An injury model was created by applying 50 N pressure to the right sciatic nerves in groups, and 10 μg/kg local PEDF was injected into the Injury+PEDF group. After 28 days of recovery, functional tests and stereological, immunohistochemical, and biochemical analyses were performed. A significant difference was found between the Injury and Injury+PEDF groups in amplitude, whereas no difference was found in latency. The number of myelinated axons and the myelinated axon area increased significantly in the Injury+PEDF group, while no statistically significant difference was found in myelin sheath thickness. Superoxide dismutase, catalase, and glutathione peroxidase activities were increased by PEDF, whereas they were suppressed in mesenchymal stem cells. PEDF exerts functional, quantitative, and antioxidative effects on sciatic nerve injury during neuroregeneration. In addition, when oxidative stress parameters were examined, it was seen that PEDF reduced oxidative stress following sciatic nerve injury.