Macrophages from C57BL/6J mice, an animal susceptible to atherosclerosis, were chosen as target cells to study changes in the transmembrane Ca2+ gradient during the formation of macrophage-derived foam cells. The transmembrane Ca2+ gradients of single living cells were examined-using Fura-2/AM combined with Fluo-3/AM by laser scanning confocal microscopy. Exposure to Oxidized Low Density Lipoprotein, decreases the Ca2+ gradient across macrophage plasma membrane, but increases that across the nuclear membrane. The altered transmembrane Ca2+ gradients could induce the up-regulation of scavenger receptor in macrophages, resulting in the formation of foam cells.