Recent studies suggest that in addition to adipocytes the chief cells of the gastric fundic mucosa are a site of leptin production. In order to assess the possible role of vagal afferent neurons in transmitting leptin signals from the stomach to the brain, leptin receptor (OB-R) expression was investigated in rat nodose ganglion cells and their projection to the stomach determined by retrograde tracing. Reverse transcription-polymerase chain reaction combined with laser-assisted cell picking revealed that large and small diameter neurons express both the long (OB-Rb) and short (OB-Ra) splice variants of the OB-R. OB-R like immunoreactivity was detected in the perikarya of approximately 8% of nodose ganglion neurons. Tracing studies revealed that a significant proportion (15%) of the immunopositive neurons projected to the gastric fundus. These findings suggest that leptin may use a neural route to relay its message from peripheral sites of leptin synthesis such as the gastric fundus to the brain.