Leptin is an adipocyte-derived cytokine that regulates body weight mainly via the long form of the leptin receptor (Ob-Rb). Leptin and its receptors are expressed in several tissues, suggesting that leptin might also be effective peripherally. We hypothesized that, as shown in taste cells, leptin and its receptors isoforms (Ob-Rs) could be present in the rat olfactory mucosa (OM). Using RT-PCR, light and electron microscopy immunohistochemistry (ICC), we found that different isoforms of the receptor were expressed in OM and localized in sustentacular cells and in a subpopulation of maturating neurons; in addition, immunoreactivity was also present in differentiated neurons and enriched at the cilia membranes, where the odorants bind to their receptors. Moreover, using RT-PCR, ICC and RIA measurements, we showed that leptin is synthesized locally in the olfactory mucosa. In addition, we demonstrate that fasting causes a significant enhanced transcription of both leptin and Ob-Rs in rat OM by quantitative RT-PCR data. Altogether, these results strongly suggested that leptin, acting as an endocrine or a paracrine factor, could be an important regulator of olfactory function, as a neuromodulator of the olfactory message in cilia of mature olfactory receptors neurons (ORN), but also for the homeostasis of this complex tissue, acting on differentiating neurons and on sustentacular cells.