An immunohistochemical study was undertaken to examine the changes of brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) in the nucleus gracilis of rats following sciatic nerve transection. The results showed that BDNF-immunoreactivity (-ir) in the gracile nucleus was significantly increased after the nerve injury. The upregulation was apparent 24 h after nerve lesion, remaining robust up to 56 days postlesion. The increase in BDNF-ir was blocked by hemisection of the spinal cord, or by dorsal rhizotomy ipsilateral to the lesion. NPY-ir changes were similar to those of BDNF-ir, but the onset was delayed by 7 days. No NPY-ir was detected in dorsal root ganglion (DRG) from normal animals. Following sciatic nerve lesion, most of the NPY-immunoreactive neurones were found to be colocalized with BDNF-immunoreactive neurones. Neutralization of endogenous BDNF with its antiserum had no effects on NPY-ir in either the gracile nucleus or DRG. These results indicate that neurones contributing to the dorsal ascending sensory pathway upregulate the expression of both BDNF and NPY in response to sciatic nerve injury.