Disclosed are a targeting aptamer for atherosclerosis and a preparation method and application thereof. The targeting aptamer is a targeting aptamer fragment for atherosclerosis obtained through screening of macrophage-derived foam cells together with reverse screening of smooth muscle cells, endothelial cells, and THP-1 cells using a SELEX method； and the use of the targeting aptamer in preparation of an MRI targeting nano-contrast agent for atherosclerosis allows the specific binding of the MRI targeting nano-contrast agent for atherosclerosis only with the macrophage-derived foam cells, and allows high specific binding thereof with vascular tissues with AS lesion, this improving targeting effect of the MRI targeting nano-contrast agent for atherosclerosis and realizing early specific diagnosis of arterial sclerosis.
