Leptin is involved in the lung epithelial homeostasis. Its role in the nasal tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen exposure leading to a consequential structural abnormalities in the nasal epithelium. Topical corticosteroids are recommended as first-line therapy in AR. Parietaria pollen is one of the most important allergenic sources in the southern Europe. In vitro on human nasal epithelial cell line RPMI 2650, we aimed to determine whether allergen stimulation acts on leptin/leptin receptor pathway and how Fluticasone Furoate (FF) influences this pathway. The effects of the major allergen rPar j 1, of FF, of leptin and of TGFβ1 on cell proliferation and on leptin/leptin receptor expression and modulation (by clonogenic test, by RT-q-RT-PCR, by immunocytochemistry and by flow-cytometry, respectively) and on STAT-3 activation (assessing nuclear translocation by western blot analysis) were assessed. We found that rPaj1 and TGFβ1 significantly decreased cell proliferation and down-regulated the leptin/leptin receptor pathway whereas leptin and FF reverted them, alone and together combined. Furthermore, rPar j 1 reduces while leptin and FF increases STAT-3 activation. In conclusion, leptin and FF are able to preserve nasal epithelial homeostasis restoring the leptin/leptin receptor pathway altered by rParj 1 exposure.