Background: There is little evidence on the efficacy of glucocorticoid transnasal nebulization therapy in patients with eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP). Objective: We sought to evaluate the immunologic and remodeling effects of budesonide transnasal nebulization in patients with eosinophilic CRSwNP. Methods: Sixty patients with eosinophilic CRSwNP were randomized to receive budesonide or placebo treatment for 14 days by means of transnasal nebulization in a double-blind manner. Endoscopic polyp size scores (maximum 5 6 points, Kennedy score) and visual analog scale scores for nasal symptoms were assessed before and after treatment. Similarly, polyp samples were evaluated for inflammatory cytokines, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) by using an immunoassay; collagen by using histochemistry; eosinophils by using hematoxylin and eosin stain; and T-cell subsets by using flow cytometry. Results: Budesonide transnasal nebulization significantly reduced polyp size compared with placebo (mean difference between groups, 20.73 units; 95% CI, -1.15 to -0.32 units; P = .002) and improved symptoms. Polyp IL-5 and eotaxin expression decreased significantly, whereas TGF-beta and IL-10 expression increased. Expression of IFN-gamma and IL-17 was not altered. Budesonide transnasal nebulization consistently reduced eosinophil infiltration and T(H)2 cell frequency and increased natural regulatory T-cell and type 1 regulatory T-cell frequencies. Indices of remodeling, including albumin, MMP-2, MMP-7, MMP-8, and MMP-9, were significantly decreased, whereas collagen deposition and TIMP-1, TIMP-2, and TIMP-4 levels were significantly increased. Budesonide transnasal nebulization did not suppress the hypothalamicpituitary-adrenal axis or cause any serious side effects. Conclusion: Short-term budesonide transnasal nebulization is an effective and safe treatment option in patients with eosinophilic CRSwNP, achieving clinical improvement by regulating remodeling, cytokine expression, and T-cell subset distribution.