To study the effect of oleate on ATP binding cassette transporter A1 (ABCA1) expression and cholesterol efflux in THP-1 macrophage-derived foam cells, after exposure of the cultured THP-1 macrophage-derived foam cells to oleate for different time, cholesterol efflux was determined by FJ-2107P type liquid scintillator. ABCA1 mRNA and its protein level were determined by RT-PCR and Western blot, respectively. The mean ABCA1 fluorescence intensity of THP-1 macrophage-derived foam cells was detected by flow cytometry. The results showed that oleate markedly inhibited ABCA1-mediated cholesterol efflux from THP-1 macrophage-derived foam cells. This was accompanied by a reduction in the membrane content of ABCA1. Oleate did not alter ABCA1 mRNA abundance, indicating that decreased ABCA1 transcription, enhanced mRNA decay, or impaired translation efficiency did not account for these inhibitory effects. Oleate, however, increased ABCA1 turnover when protein synthesis was blocked by cycloheximide. Oleate reduces cholesterol efflux and the level of ABCA1 protein in THP-1 macrophage-derived foam cells.