Macrophages have been identified as a critical factor in the pathogenesis of atherosclerosis. Ultrasmall iron oxide particles (USPIOs) have been used to passively target intraplaque macrophages. For dextran-based USPIOs, uptake into macrophages may be modulated by particle size. The aim of the current study was to test the efficacy of fractionated Feridex with respect to macrophage uptake in atherosclerotic rabbits. Fractionation of Feridex resulted in a 15-nm USPIO that exhibited a blood half-life of 15.9 h and liver retention of 6.4%. Blood clearance and liver retention of Feridex was 0.46 h and 60%, following administration of 4.8 mg Fe/kg Feridex. Atherosclerotic rabbits were administered 0.5 or 4.8 mg Fe/kg dosages of either fractionated Feridex or Feridex. MRI was performed at 1.5T over a 24-h time period postinjection. Perls and RAM-11 staining was performed to identify iron deposition. MRI showed a dose-dependent signal loss using conventional gradient echo (GRE) sequences following administration of fractionated Feridex. Even at low dose, significant signal loss was observed that correlated with histology. No signal attenuation or iron deposition was observed in the vessel wall of rabbits administered Feridex. Results of this study suggest that it may be possible to optimize USPIOs for intraplaque macrophage detection.