Objective and design <p>This study aimed to investigate the role of pyruvate kinase muscle isoform 2 (PKM2) in macrophage-driven allergic rhinitis (AR) pathogenesis using both in vivo and in vitro experimental models.</p> Material or subjects <p>Myeloid-specific PKM2 knockout (PKM2^mye−KO) and littermate control (PKM2^WT) mice were used, along with human nasal mucosa samples from AR patients and bone marrow-derived macrophages (BMDMs).</p> Treatment <p>BMDMs were treated with the PKM2 activator TEPP-46 (100 µM) or vehicle prior to house dust mite (HDM) stimulation.Methods: Histological and immunological analyses were performed on human and murine tissues. Cytokine expression, nuclear translocation, and metabolic markers were assessed in BMDMs following HDM stimulation. Statistical significance was evaluated using appropriate tests (e.g., Student’s t-test or ANOVA).</p> Results <p>PKM2 levels and macrophage infiltration were elevated in AR patient nasal mucosa. PKM2^mye−KO mice showed reduced allergic inflammation, decreased pro-inflammatory cytokines (e.g., IL-6, TNF-α), and suppressed STAT3 activation compared to controls. TEPP-46 treatment attenuated HDM-induced cytokine release and nuclear PKM2 translocation.</p> Conclusions <p>PKM2 regulates macrophage-mediated inflammation in AR via STAT3-dependent pathways, suggesting its nuclear translocation and interaction with STAT3 as potential therapeutic targets for allergic diseases.</p>