This study investigates the role of Ly-6C^hi^ monocytes in hypercholesterolemia-associated monocytosis and their transformation into macrophages in atheromatous plaques. The research was conducted on apoE-deficient mice fed a high-fat diet, which led to a significant increase in Ly-6C^hi^ monocytes in the blood, with a doubling every month. These monocytes adhered to activated endothelium, infiltrated lesions, and differentiated into lesional macrophages. Hypercholesterolemia-associated monocytosis (HAM) was characterized by increased survival, continued proliferation, and impaired conversion of Ly-6C^hi^ to Ly-6C^lo^ monocytes. The study also found that statin treatment reduced monocytosis and atherosclerosis. The results suggest that Ly-6C^hi^ monocytes are a key component of the inflammatory response in atherosclerosis and that their accumulation and differentiation into macrophages contribute to plaque formation and progression.This study investigates the role of Ly-6C^hi^ monocytes in hypercholesterolemia-associated monocytosis and their transformation into macrophages in atheromatous plaques. The research was conducted on apoE-deficient mice fed a high-fat diet, which led to a significant increase in Ly-6C^hi^ monocytes in the blood, with a doubling every month. These monocytes adhered to activated endothelium, infiltrated lesions, and differentiated into lesional macrophages. Hypercholesterolemia-associated monocytosis (HAM) was characterized by increased survival, continued proliferation, and impaired conversion of Ly-6C^hi^ to Ly-6C^lo^ monocytes. The study also found that statin treatment reduced monocytosis and atherosclerosis. The results suggest that Ly-6C^hi^ monocytes are a key component of the inflammatory response in atherosclerosis and that their accumulation and differentiation into macrophages contribute to plaque formation and progression.