The objective was to dynamically monitor the progression of atherosclerotic plaques in ApoE-/- mice with 18F-NaF PET imaging. The ApoE-/- mice were used to develop atherosclerosis models, and the C57BL/6J mice were used as control. 18F-NaF PET was performed when the mice were 12, 20, and 30weeks of age. Serum lipids and lipoproteins profiles, inflammatory cytokines, and calcification factors were tested by ELISA. The lipid distribution, morphology, and calcification of plaque were evaluated by Oil Red O, HE, and alizarin red staining. The correlation between imaging and the extent of calcification was analyzed by Pearson correlation analysis. The uptake of 18F-NaF in the aorta was gradually increased with each weekly extension. Compared with the ApoE-/- mice at the age of 12weeks and 20weeks, the levels of lipoprotein, inflammatory cytokines, and calcification factors were higher at 30weeks. In Oil Red O, HE, and alizarin red staining, the extent of the lipid area and calcification increased with time. The correlation analysis showed that the uptake of 18F-NaF in the aorta was related to the extent of calcification. 18F-NaF may dynamically monitor the progression of atherosclerotic plaques and ongoing microcalcification formation.