Introduction: Charcot-Leyden crystal (CLC) protein has been regarded as a hallmark of eosinophilic inflammation. Objective: The purpose of this study was to investigate the role and levels of CLC protein in patients with nonallergic rhinitis with eosinophilia syndrome (NARES). Methods: Overall, 39 NARES patients and 19 controls were recruited. The severity of nasal symptoms was measured by visual analogue scale and serum and local specific immunoglobulin E were determined in all patients. Nasal eosinophilia was assessed by semiquantitative analysis of eosinophils in nasal scrapings. Nasal secretion CLC protein concentrations were evaluated by ELISA. Results: CLC protein concentrations were significantly higher in NARES patients than in controls (p < 0.0001). Nasal secretion CLC protein levels were significantly correlated with the degree of eosinophilia in nasal scrapings (rsub>s = 0.331; p = 0.04) in NARES patients. Patients with high CLC protein concentrations displayed more severe nasal symptoms than patients with low CLC protein concentrations (p = 0.0080), particularly, nasal itching (p = 0.0029). Pilot study in 8 NARES patients demonstrated that treatment for 1 month with intranasal fluticasone propionate significantly decreased the nasal secretion CLC protein concentrations from baseline levels (p = 0.0335) and markedly attenuated the degree of swelling of inferior turbinate. Conclusions: CLC protein levels are significantly higher in nasal secretions of NARES patients and associated with the degree of nasal eosinophilia and the severity of nasal symptoms. Significantly, nasal secretion CLC protein levels obviously decreased after treatment with intranasal corticosteroids, suggesting its possible role in evaluating the medical treatment.