Atherosclerosis is a chronic inflammatory disease characterized by lipid streaks, which are produced by aggregates of lipid-rich foam cells. Foam cells intensify atherosclerosis by secreting a range of inflammatory mediators. Neutrophil extracellular traps produced by activated neutrophils, which are abundantly present in lipid-accumulating plaques. However, the relationship between neutrophil extracellular traps and foam cells inflammation is still unclear. Paeonol is well known for its anti-inflammatory effects in atherosclerosis. Nevertheless, the exact pharmacological mechanisms by which paeonol affects atherosclerosis are not fully understood which require further investigation. The purpose of this study is to investigate the effects of paeonol on the neutrophil extracellular traps' formation and foam cell inflammation caused by neutrophil extracellular traps, and to explore the potential mechanisms. A high-fat diet was administered to ApoE