Aim To investigate the mechanism of ezetimibe-induced cholesterol efflux by observing the effect of ezetimibe on ATP binding cassettet transporter A1 and Liver X Receptor α in lipid-loaded cells derived from vascular smooth muscle cell(VSMC). Methods Lipid-loaded cell model was established with the mix of 20 mg/L Chol∶MβCD treating VSMC. Lipid-loaded cells were treated with different concentration of ezetimibe(3,10,30 μmol/L)for 24 hours respectively,and 30 μmol/L ezetimibe was selected for lipid-loaded cell treatment of different time respectively (0,6,12,24,48 h). ATP binding cassettet transporter-A1 mRNA was detected by reverse transcription PCR(RT-PCR) and the protein expression of Liver X Receptor α was examined by Western-blotting. Results (1) With different concentration of ezetimibe treated lipid-loaded cells,the mRNA expression of ATP binding cassettet transporter-A1 increased with concentration. Compared with the model group,the 30 μmol/L ezetimibe-treated group (24 h ) had a 3.4 folds rising. Treated with 30 μmol/L ezetimibe for different time(0,6,12,24,48 h),the mRNA expression of ATP binding cassettet transporter-A1 had a time dependant trend reaching plateau at 24 h and the best concentration was 30 μmol/L. (2) With different concentration of ezetimibe treated lipid-loaded cells,the protein expression of Liver X Receptor α increased with rising concentration. Compared with the model group,the 30 μmol/L ezetimibe-treated group(24 h) had an increase of more than 2 folds. Treated with 30 μmol/L ezetimibe for different time(0,6,12,24,48 h),the protein expression of Liver X Receptorα had a time dependant trend with 24 h reaching plateau and the best time was 24h. Conclusion Ezetimibe promotes cellular cholesterol efflux in lipid-loaded cells derived from VSMC by up-regulating Liver X Receptorα and ATP binding cassettet transporter-A1 expression.