Chronic obstructive pulmonary disease (COPD) is a disease with severe therapeutic obstacles and high worldwide death rate. COPD progresses predominantly through an inflammatory response followed by fibrotic destruction. Quercetin (Que), recognized for its anti-inflammatory effects, presents significant promise as a therapeutic agent for COPD therapy. However, poor water solubility and low bioavailability of Que hinder its further clinical application. To address these issues, we developed Que liposomes (Que-lipo) to improve the solubility and bioavailability of Que. Que-lipo showed a gradual and sustained Que release profile in vitro, coupled with high biocompatibility and cellular uptake. Upon intratracheal administration, it showed significantly alleviate lung inflammation and fibrosis symptoms in a COPD mouse model. By modulating the inflammatory factor expression, antioxidant enzyme activity, and apoptosis-related proteins, Que-lipo significantly reduced oxidative stress and cell apoptosis. Que-lipo also exhibited anti-inflammatory and antifibrotic features by suppressing the NLRP3/IL-1β inflammasome pathway and TGF-β1 fibrosisrelated signaling pathway. Overall, this study offers novel insights and strategies for the treatment of COPD, as well as provides innovative approaches for the application of Que.