This study examined the accumulation of superparamagnetic iron oxide (SPIO) nanoparticles in vulnerable atherosclerotic plaques. In vitro experiments demonstrated that human macrophages actively take up fluorescent-labeled SPIO particles over 24 hours in a time- and concentration-dependent manner. In vivo studies in mice and rabbit models of atherosclerosis found SPIO particles in macrophage-rich areas of plaques, with a strong correlation between iron staining and foam cell density. Cytokine treatment increased SPIO uptake in plaques. The results suggest MRI using SPIO has potential for noninvasively assessing monocyte recruitment in vulnerable plaques.