Monocytes play a critical role in atherosclerosis, and their recruitment to atherosclerotic plaques is influenced by chemokine receptors. This study investigates the differential usage of chemokine receptors CCR2, CCR5, and CX3CR1 by two major monocyte subsets in apoE-deficient mice. Monocyte subsets were labeled with latex beads and tracked in vivo to assess their entry into atherosclerotic plaques. Results show that both Ly-6C^hi^ (classical) and Ly-6C^lo^ (nonclassical) monocyte subsets enter plaques, with the classical subset being more efficient. Classical monocytes rely on CCR2 and CX3CR1 for entry, while the nonclassical subset uses CCR5. Neutralization of CCR5 significantly reduced the entry of Ly-6C^lo^ monocytes into plaques, suggesting that targeting CX3CR1 may be more effective in reducing plaque progression without impairing overall monocyte responses to inflammation. The study also highlights the potential role of CX3CR1 in monocyte recruitment and the heterogeneity of macrophages within plaques, with Ly-6C^lo^ monocytes more likely to differentiate into CD11c+ cells.Monocytes play a critical role in atherosclerosis, and their recruitment to atherosclerotic plaques is influenced by chemokine receptors. This study investigates the differential usage of chemokine receptors CCR2, CCR5, and CX3CR1 by two major monocyte subsets in apoE-deficient mice. Monocyte subsets were labeled with latex beads and tracked in vivo to assess their entry into atherosclerotic plaques. Results show that both Ly-6C^hi^ (classical) and Ly-6C^lo^ (nonclassical) monocyte subsets enter plaques, with the classical subset being more efficient. Classical monocytes rely on CCR2 and CX3CR1 for entry, while the nonclassical subset uses CCR5. Neutralization of CCR5 significantly reduced the entry of Ly-6C^lo^ monocytes into plaques, suggesting that targeting CX3CR1 may be more effective in reducing plaque progression without impairing overall monocyte responses to inflammation. The study also highlights the potential role of CX3CR1 in monocyte recruitment and the heterogeneity of macrophages within plaques, with Ly-6C^lo^ monocytes more likely to differentiate into CD11c+ cells.