Nasal eosinophilic inflammation is the therapeutic target for olfactory dysfunction in allergic rhinitis (AR). Intranasal corticosteroids are commonly considered to offer targetable benefit given their immunosuppressive property. However, experimental evidence suggests that continuous corticosteroid exposure may directly cause olfactory damage by disrupting the turnover of olfactory sensory neurons (OSNs). This potentially deleterious effect of corticosteroids calls into question their long-term topical use for treating olfactory loss related to AR. The aim of this study was to assess the impacts of chronic intranasal corticosteroid treatment on olfactory function and OSN population in mice under normal and pathological conditions.BALB/c mice were intranasally treated with fluticasone propionate (FP, 0.3 mg/kg) for up to 8 weeks. Additional mice were used to establish an ovalbumin-induced mouse model of AR, followed by nasal challenge with ovalbumin for 8 weeks in the presence or absence of intranasal FP treatment. We examined olfactory function, OSN existence, neuronal turnover, and nasal inflammation using the behavioral test, histological analyses, Western blotting, and enzyme-linked immunosorbent assay.Intranasal treatment with FP for 8 weeks (FP-wk8) reduced odor sensitivity in normal mice. This reduction was concomitant with loss of OSNs and the axons projecting to the olfactory bulb, primarily resulting from increased neuronal apoptosis. In FP-wk8 AR mice, intranasal FP treatment attenuated olfactory impairment and eosinophilic inflammation, but failed to reconstitute OSN population and axonal projections.Our results suggest that chronic intranasal corticosteroid treatment contributes to OSN degeneration that may reduce the therapeutic effectiveness for AR-related olfactory loss. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.