Intake of saturated and trans-fatty acids is a strong risk factor for coronary heart disease. We investigated the inhibitory effects of 2 hexane extracts from white (WBE) and black soybeans (BBE) on cellular fatty acid uptake in vitro. Transcellular uptake of elaidic acid (t18:1), a major trans-fatty acid present in processed foods, in Caco-2 monolayers was significantly reduced by 28.3 and 16.7% 60 min after WBE and BBE treatment, respectively. Results of flow cytometry (FACS) analysis showed significant reductions in boron-dipyrromethene (BODIPY) fluorescencelabeled fatty acid uptake by 35.4 and 40.2% with WBE and BBE treatment, respectively. BBE treatment significantly reduced the expression of fatty acid transport protein-4 and CD36 in Caco-2 cells, as determined by quantitative real time-polymerase chain reaction (qRT-PCR). Similar trends were found in WBE treatment, although to a lesser degree. These observations suggest that soybean extract may reduce fatty acid uptake and cellular fat accumulation by altering fatty acid transporter expression.