Background: Apolipoprotein A-I (ApoA-I), the major protein component of high-density lipoprotein, is increasingly recognized for its immunomodulatory roles beyond lipid transport, including antimicrobial and anti-inflammatory functions. Although ApoA-I can modulate immune cell activity, its effect on eosinophils remains poorly understood. Objective: This study aimed to determine whether ApoA-I could modulate human eosinophil activation and survival during fungal stimulation and to elucidate the underlying mechanisms. Methods: Human eosinophils were isolated and stimulated with Alternaria alternata or β-glucan in the presence or absence of recombinant ApoA-I. Eosinophil degranulation was assessed by measuring eosinophil-derived neurotoxin (EDN) release using an enzyme-linked immunosorbent assay. Surface CD11b expression and cell viability were evaluated using flow cytometry. Dose-response experiments and comparisons with apolipoprotein A-II (ApoA-II) and interleukin-5 (IL-5) were also conducted. Results: ApoA-I markedly increased EDN secretion and upregulated CD11b expression upon fungal stimulation. It also improved eosinophil viability, with effects comparable to those of IL-5. These responses were specific to ApoA-I, as ApoA-II did not elicit similar effects. Conclusion: ApoA-I enhanced eosinophil activation and survival following fungal stimulation. These findings underscore the context-dependent immunomodulatory role of ApoA-I and its potential as a regulator of antifungal immunity. (Korean J Dermatol 2025;63(6):155∼164)