Aim To investigate and compare the effects of aminolevulinic acid (ALA)-mediated sonodynamic therapy (SDT) on macrophages and foam cells. Methods The THP-1 cells were differentiated into macrophages by adding phorbol-12-myristate-13-acetate, and then the macrophages were differentiated into foam cells by adding oxidized low density lipoprotein. The two kinds of cells were used to study. The protoporphyrin Ⅸ fluorescence intensity were observed after the cells incubated with ALA; The two kinds of cells were divided into control and SDT groups respectively, the following indicators were detected:reactive oxygen, mitochondrial membrane potential, cell apoptosis and the enzyme activity of caspase-9,3. Results Red PpⅨ fluorescence were observed in both macrophages and foam cells after incubation with ALA for three hours. The fluorescence of foam cells was stronger, but there was no statistical difference(P＞0.05); The reactive oxygen of macrophages and foam cells increased 1.84 (P＜0.01) and 1.44 (P＜0.001) times respectively after SDT; Cells with low mitochondrial membrane potential increased 1.96(P＜0.001) and 1.55(P＜0.001) times respectively; The apoptosis rate increased 1.36(P＜0.001) and 2.78 (P＜0.001) times respectively; The enzyme activity of caspase-9 increased 1.34(P＜0.05) and 2.59(P＜0.001) times; And the enzyme activity of caspase-3 increased 2.97(P＜0.01) and 4.88(P＜0.001) times respectively. Conclusion ALA-mediated SDT had apoptotic effects on THP-1 macrophages and foam cells via generation reactive oxygen and damaging mitochondrial, activating caspase apoptosis pathway. It is more effective to foam cells. ALA-mediated SDT may be a potential treatment to attenuate progression of atherosclerotic plaque.