Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipoproteins and inflammatory cells in the arterial intima. The balance between pro-inflammatory and inflammation-resolving mechanisms determines the clinical outcome. Inflammation resolution is mediated by specialized pro-resolving lipid mediators, proteins, and signaling gases. Defective efferocytosis, a sign of inadequate inflammation resolution, leads to the accumulation of necrotic macrophages and foam cells, forming advanced lesions with a necrotic lipid core. The ratio of pro-resolving lipid mediators to pro-inflammatory lipids is low in advanced atherosclerotic lesions, contributing to defective inflammation resolution. This review discusses the mechanisms of atherosclerotic lesion formation and the potential of pro-resolving mediator therapy to inhibit this process. Lipoprotein modification, NLRP3 inflammasome activation, and macrophage life cycle are key factors in atherosclerosis. Pro-resolving mediators, such as resolvins, lipoxins, maresins, and protectins, can inhibit the NLRP3 inflammasome and promote efferocytosis, reducing inflammation and plaque progression. Targeting inflammation resolution pathways, including pro-resolving receptor signaling, may offer new therapeutic opportunities for atherosclerosis.Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipoproteins and inflammatory cells in the arterial intima. The balance between pro-inflammatory and inflammation-resolving mechanisms determines the clinical outcome. Inflammation resolution is mediated by specialized pro-resolving lipid mediators, proteins, and signaling gases. Defective efferocytosis, a sign of inadequate inflammation resolution, leads to the accumulation of necrotic macrophages and foam cells, forming advanced lesions with a necrotic lipid core. The ratio of pro-resolving lipid mediators to pro-inflammatory lipids is low in advanced atherosclerotic lesions, contributing to defective inflammation resolution. This review discusses the mechanisms of atherosclerotic lesion formation and the potential of pro-resolving mediator therapy to inhibit this process. Lipoprotein modification, NLRP3 inflammasome activation, and macrophage life cycle are key factors in atherosclerosis. Pro-resolving mediators, such as resolvins, lipoxins, maresins, and protectins, can inhibit the NLRP3 inflammasome and promote efferocytosis, reducing inflammation and plaque progression. Targeting inflammation resolution pathways, including pro-resolving receptor signaling, may offer new therapeutic opportunities for atherosclerosis.