Oxidized low-density lipoprotein (ox-LDL) is a critical mediator of atherogenesis. Macrophage uptake of ox-LDL and their subsequent development into foam cells is the principal event in atherosclerosis. Interleukin-1 beta (IL-1 beta), a prototypic multifunctional cytokine involved in inflammation, has an important effect on the pathogenesis and progression of atherosclerosis. Here we show that the phagocytosis of ox-LDL can induce human macrophages to secrete IL-1 beta by activating the NLRP3 inflammasome, and we further show that the activation of the NLRP3 inflammasome is dependent on the generation of reactive oxygen species and is related to the cathepsin B pathway. Furthermore, ox-LDL can upregulate the expression of the pro-IL-1 beta protein, thus priming IL-1 beta secretion. Therefore, our results suggest that the role of ox-LDL in atherosclerosis-related inflammation may involve the activation of the NLRP3 inflammasome. Crown Copyright (c) 2012 Published by Elsevier Inc. All rights reserved.