Abstract: Objective To explore the effects and the possible mechanisms of retinoid X receptor α（RXRα） agonist bexarotene on Wnt and β-catenin and arteriosclerosis in apolipoprotein E knockout(ApoE^-/-) mice. Methods In animal experiments, eight C57 mice were used as normal control group（NCG）, and twenty-four ApoE^-/- mice were randomly divided into 3 groups: ApoE^-/- group, ApoE^-/-+high fat chow group（to establish atherosclersis mouse model） group and ApoE^-/-+high fat chow+Bex10 gavage group intervention with bexarotene 10 mg/（kg·d） for 3 months. Blood lipid levels were detected. Patch area in thoracic aorta was measured by HE staining. Wnt and β-catenin protein levels were detected by immunoblotting. For in vitro experiments, thoracic aorta vascular smooth muscle cells（VSMC） were cultured, and experiments were carried out as following: the Wnt and β-catenin protein level of cells was detected after intervention with platelet derived growth factor（PDGF）（0, 1, 3, 10, 30 ng/mL） for 24 hours, or after intervention with PDGF（10 ng/mL） and RXRα agonist 9-cis-retinoic acid（9 cis-RA） 10^-7 mol/L for 24 hours. The proliferation level of VSMC was measured by 5-bromodeoxyuridine（BrdU） infiltration method after intervention with PDGF（10 ng/mL）, 9 cis-RA 10^-7 mol/L and β-catenin inhibitor FH535(10^-6 mol/L) for 24 hours. Cell migration was measured by membrane migration method after intervention with PDGF（10 ng/mL）, 9-cis-RA 10^-7 mol/L and FH535(10^-6 mol/L) for 4 hours. Results Compared with C57 BL/6 mice, triglyceride, total cholesterol, and low-density lipoprotein cholesterol（LDL-C） levels were increased in ApoE^-/- mice and increased further in ApoE^-/-+ high fat chow mice. Compared with C57 BL/6 group, patch area in thoracic aorta （64.29±9.87） vs 0 μm~2, P＜0.05 and Wnt and β-catenin protein levels were increased in ApoE^-/-mice. Compared with ApoE^-/-+ high fat chow group, patch area in thoracic aorta （124.09±15.42） vs（218.86±15.79）μm~2, P＜0.05, Wnt and β-catenin protein levels decreased in ApoE^-/-+high fat chow+Bex10 group. Compared with PDGF（0 ng/mL）group, Wnt and β-catenin protein levels, VSMC proliferation and migration levels in PDGF（10 ng/mL） group were all increased. Compared with PDGF（10 ng/mL） group, Wnt and β-catenin protein levels, VSMC proliferation and migration levels in PDGF（10 ng/mL）+9-cis-RA(10^-7 mol/L) group were all decreased. There was no statistical significance of VSMC proliferation and migration levels in PDGF（10 ng/mL）+β-catenin inhibitor FH535 group and PDGF（10 ng/mL） +9-cis-RA(10^-7 mmol/L) group. Conclusions RXRα agonists decrease Wnt and β-catenin level, suppress VSMC proliferation, migration, and improve atherosclerosis. The mechanism of anti-atherosclerosis by RXRα agonist can be mediated by Wnt-β-catenin.