Aim To investigate the effects and mechanisms of cyclophilin A (CypA) on the expression of ATP binding cassette trasporter A1 (ABCA1) and cholesterol efflux in THP-1 derived macrophages. Methods THP-1 cells were incubated with 160 nmol/L phorbol ester to transform into macrophages. THP-1 derived macrophages were exposed to 50 mg/L oxidized low density lipoprotein (ox-LDL) and cultured with typical approaches. Liquid scintillation counter was used to determine the efficiency of cholesterol efflux. Lipids contents were tested with high performance liquid chromatogram (HPLC). Real-time PCR and Western blot were used to quantify the expression of ABCA1 and nuclear factor-κB (NF-κB) nuclear translocation. Parthenolide was used as the specific inhibitor of NF-κB. CD147 was silenced with siRNA. Results CypA significantly reduced cholesterol efflux, promoted NF-κB nuclear translocation and downregulated ABCA1 expression. NF-κB inhibitor parthenolide interfered CypA-prevented ABCA1 expression and cholesterol efflux. After CD147 were silenced with siRNA, CypA inhibited NF-κB nuclear translocation, upregulated ABCA1 expression and promoted cholesterol efflux. Conclusion CypA prevented THP-1 derived macrophages cholesterol efflux by activing NF-κB in a CD147 dependent manner and downregulating ABCA1 expression.