Aim To investigate the effects and mechanisms of nuciferine (NF) on the expression of ATP binding cassette transporter A1 (ABCA1) and cholesterol efflux in THP-1 macrophages-derived foam cells. Methods THP-1 cells were differentiated into macrophages by 160 nmol/L phorbol myristate acetate. THP-1 derived macrophages were incubated with 50 mg/L oxidized low density lipoprotein to induce foam cells and cultured with typical approaches. Lipids contents were tested with high performance liquid chromatogram. Liquid scintillation counter was used to determine the efficiency of cholesterol efflux. Real-time PCR and Western blot were used to quantify the expression of ABCA1. The THP-1 macrophages derived foam cells were pretreated with peroxisome proliferator-activated receptor γ (PPARγ) inhibitor GW9662 or LXRα inhibitor GGPP to detect the expression of ABCA1 by real-time quantitative PCR and Western blot. Results NF obviously reduced the intracellular Lipids contents, increased the ABCA1 expression and cholesterol efflux in THP-1 macrophages derived foam cells. PPARγ inhibitor GW9662 and LXRα inhibitor GGPP both interfered NF-promoted ABCA1 expression. Conclusion NF up-regulates the expression of ABCA1 by PPARγ/LXRα pathway to promote the cholesterol efflux and reduce the lipid accumulation in THP-1 macrophages derived foam cells.