Background: We recently synthesized organic dye-incorporated silica coated core-shell fluorecent magnetic nanoparticles (FMNP). Macrophages play an crucial role in the pathogenesis of plaque inflammation and vulnerability. We compared the cellular uptake of FMNP in atherosclerotic cell lines and then evaluated whether FMNP could provide in vivo MR imaging of atherosclerotic plaques in apolipoprotein E (apoE)-deficient mice. Methods: FMNP uptake into human primary endothelial cells, aortic vascular smooth muscle cells, and activated macrophages was quantified by confocal laser scanning microscopy (CLSM). In vivo experiments were performed in 2% cholesterol-fed apoE-deficient mice treated with angiotensin II (n=5). FMNP (40 mg/kg) was injected via tail vein and then in vivo MRI (4.7T) was obtained 24 hours later. Atheroma then underwent CLSM and immunohistochemical staining targeted to macrophages. Results: Preferential uptake of FMNP by activated macrophages than any other cells was observed in CLSM images (p<0.05). In vivo MRI demonstrated strong enhancement of atherosclerotic plaques in the aortic root by FMNP compared with precontrast images (signal intensity 1.69짹0.3 vs 1.0 p<0.01). Histologic examination showed preferential localization of FMNP in lesional macrophages. Conclusion: Silica coated FMNP might function as an effective multimodal imaging agent in the identification of inflammation in atherosclerotic plaques.