Abstract: Objective :To investigate the reversal efficacy of ultrasonic (US) therapy on multidrugresistance (MDR) in HepG2/ADM cells in vivo and to study the underlying mechanism. Methods :Atotal of 70 nude mice bearing HepG2/ADM tumors were randomized into the control group(n=10), ADMgroup(n=20), US group(n=20), and ADM plus US group(n=20). Tumor specimens were collected fromthe mice in each group 28 days after the interventions. Expression of the MDR-related genes MDR1,MDR resistance-associated protein (MRP) and lung resistance protein (LRP) were assayed by reversetranscription-polymerase chain reaction(RT-PCR) and immunohistochemistry. Results :US significantlyreversed MDR in HepG2/ADM cells in nude mice. Immunohistochemistry showed that expression of P-gp and MRP was significantly reduced in the US group and the ADM plus US group. Decreased ex-pression of MDR1 and MRP mRNA in HepG2/ADM tumor cells was detected by RT-PCR in the USgroup and the ADM plus US group. Conclusion :US has strong reversal effects on MDR in HepG2/ADM cells through multiple routes including downregulating MDR1 and MRP mRNA and protein ex-pression and increasing intracellular drug concentration.