Leptin is involved in the lung epithelialhomeostasis. Its role in the nasal tract is largely unknown.Allergic rhinitis (AR) is induced by the allergen exposureleading to consequential structural abnormalities in thenasal epithelium. Topical corticosteroids are recommendedas first-line therapy in AR. Parietaria pollen is one of themost important allergenic sources in the southern Europe.In vitro, in human nasal epithelial cell line RPMI 2650, weaimed to determine whether allergen stimulation acts onleptin/leptin receptor pathway and how fluticasone furoate(FF) influences this pathway. The effects of the majorallergen recombinant Par j 1 (rPar j 1), of FF, of leptin, andof TGF-b1 on cell proliferation, on leptin/leptin receptorexpression and modulation (by clonogenic test, by RT-q-RT-PCR, by immunocytochemistry and by flow-cytometry),and on STAT-3 activation (assessing nucleartranslocation by western blot analysis) were assessed. Wefound that rPar j 1 and TGF-b1 significantly decreased cellproliferation and down-regulated the leptin/leptin receptorpathway, whereas FF and leptin reverted them, both aloneand in combination. Furthermore, rPar j 1 reduced, whileleptin and FF increased STAT-3 activation. In conclusion,FF and leptin itself are able to preserve nasal epithelialhomeostasis restoring the leptin/leptin receptor pathwayaltered by rPar j 1 exposure.