OBJECTIVE The aim of the study was to examine the reversal eě ects of ultrasound (US) on the MDR in HepG 2 /ADM, a HepG 2 cell line resistant to Adriamycin (ADM), and to study the mechanism of US action. METHODS Using the MTT assay, the eě ects of US on MDR in HepG 2 /ADR cells were studied. Before and after the treatment with 0.5 W/cm 2 low intensity ultrasound (LIUS), the expression of the MDR-related genes, mdr1, mrp and lrp was assayed with the reverse transcriptase polymerase chain reaction (RT-PCR) and the levels of their respective protein expression determined by flow cytometry. By using confocal laser scanning microscopy (CLSM), we examined the intracellular daunorubicin (DNR) distribution, and the eě ects on the cells of treatment with US or DNR. RESULTS LIUS significantly reversed MDR in HepG 2 /ADR cells. AĞ er treatment with LIUS at 0.5 W/cm 2 , chemosensitivity to ADM and DNR increased 3.35-fold and 2.81-fold, respectively. The reversal activity by LIUS plus verapamil (VER) was stronger than with either US or VER alone. AĞ er treatment with 0.5 W/cm 2 , the expression of both the MDR1 and the MRP mRNA genes began to decline (P < 0.01 and P < 0.05, respectively); the expression of LRP showed no significant changes. Changes in the expression of the P-glycoprotein (P-gp) and MRP were similar to those of their mRNA expressions. Results of the CLSM showed that administration of US (0. 5 W/cm 2 ) or VER (15.7 ΐM) with DNR to HepG 2 /ADM cells showed a signię cant change in the distribution of DNR in the cells. CONCLUSION Our results show that LIUS can reverse MDR. The reversal effects are stronger than those of either US or VER alone, when combined with VER administration. As LIUS is noninvasive causing no toxicity, it might have potential for clinical application. The reversal mechanism needs further study.