Antroquinonol (Antroq) is an active component of Antrodia camphorate. The present study was to validate the preventive effects of Antroq in an atherosclerosis model. Materials and Methods: We examined Antroq inhibitory effect on rat aortic smooth muscle cell proliferation and migration and evaluated its effect on neointima formation and inflammation in mouse carotid artery ligation (CAL). Results: Our data show that Antroq inhibited the proliferation (Antroq [3.0 μg/ml] + PDGF 41.7 ± 7.3%, vehicle + PDGF 134.5 ± 7.3%) (p ＜ 0.005) and migration (6h: Antroq [3.0 μg/ml] + PDGF 0.9 ± 0.3%, vehicle + PDGF 25.0 ± 3.4%; 12h: Antroq [3.0 μg/ml] + PDGF 4.0 ± 1.6%, vehicle + PDGF 40.5 ± 2.2%; 24h: Antroq [3.0 μg/ml] + PDGF 14.2 ± 3.0%, vehicle + PDGF 59.8 ± 3.3%) (each, p ＜ 0.005) of the cultured smooth muscle cells, prevented neointima formation and reduced N/M ratios in CAL mice (900 μm: Antroq + CAL 0.8 ± 0.3, CAL 3.5 ± 1.1; 800 μm: Antroq + CAL 0.6 ± 0.2, CAL 3.5 ± 0.7; 700 μm: Antroq + CAL 0.7 ± 0.2, CAL 3.8 ± 0.4; 600 μm: Antroq + CAL 0.9 ± 0.2, CAL 3.8 ± 0.9; 500 μm: Antroq + CAL 1.3 ± 0.4, CAL 3.9 ± 0.8; 400 μm: Antroq + CAL 1.5 ± 0.5, CAL 4.0 ± 1.0; 300 μm: Antroq + CAL 1.8 ± 0.6, CAL 3.5 ± 0.6; 200 μm: Antroq + CAL 2.3 ± 0.6, CAL 4.6 ± 1.1) (each, p ＜ 0.01), and prevented inflammatory processes and matrix accumulation/fibrosis in the CAL mice. Conclusions: Our data may be useful in developing new and practical strategy for the prevention of atherosclerosis based on the pathogenesis of the disorder.