Distraction osteogenesis (DO) has become the mainstay of treatment of mandibular hypoplasias. Despite the clinical acceptance of the technique in the last decade, little is known of the biological mechanism of bone and soft tissue regeneration. The biological response of peripheral nerves to distraction has not been well documented. This study examined the role of two neurotrophic molecules, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), in DO on nerve regeneration of the inferior alveolar nerve (IAN) in an ovine mandible model. Twelve animals were randomly divided into three groups and distracted at 5, 10, and 15 days using a mandibular osteotomy and uniaxial external distractor. The mental nerves and the IAN from the distracted site were harvested at the end of the distraction period and examined for the presence of NGF and BDNF using immunohistochemistry. Nerve growth factor expression was increased at both sites, whereas BDNF was only expressed at the mental nerve on the distracted side. Nerve growth factor and BDNF are involved in the response of the peripheral nerves to injury. Mechanical force applied to the IAN by distraction may lead to detachment of Schwann cells from their axons, leading to segmental degeneration. The resulting myelin sheath debris may serve as a trigger for higher expression of NGF and BDNF, facilitating Schwann cell proliferation and remyelination of the affected segment. Distraction of the mandible may serve as a source of subacute injury to the IAN and influence NGF and BDNF.