AIM:To investigate the pathological characteristics of non-thermal damage induced by pulsed high intensity focused ultrasound (PHIFU) combined with ultrasound contrast agent (UCA),SonoVue (Bracco SpA,Milan, Italy) in rabbit liver VX2 tumor. METHODS:Liver VX2 tumor models were established in 20 rabbits,which were divided randomly into PHIFU combined with ultrasound contrast agent group (PHIFU +UCA group) and sham group.In the PHIFU+UCA group,0.2 mL of SonoVue was injected intravenously into the tumor,followed by ultrasound exposure of I_(SP) 5900 W/cm~2.The rabbits were sacrificed one day after ultrasound exposure.Specimens of the exposed tumor tissues were obtained and observed pathologi- cally under light microscope and transmission electron microscope.The remaining tumor tissues were sent for 2,3,5-Triphenyltetrazolium chloride (TTC) staining. RESULTS:Before TTC staining,tumor tissues in both the sham and the PHIFU+UCA groups resembled gray fish meat.After TTC staining,the tumor tissues were uniformly stained red,with a clear boundary between tumor tissue and normal tissue.Histological examina- tion showed signs of tumor cell injury in PHIFU+UCA group,with cytoplasmic vacuoles of various sizes,chro- matin margination and karyopyknosis.Electron micro- scopic examination revealed tumor cell volume reduc- tion,karyopyknosis,chromatin margination,intercellular space widening,the presence of high electron-density apoptotic bodies and vacuoles in cytoplasm. CONCLUSION:The non-thermal effects of PHIFU combined with UCA can be used to ablate rabbit liver VX2 tumors. To investigate the pathological characteristics of non-thermal damage induced by pulsed high intensity focused ultrasound (PHIFU) combined with ultrasound contrast agent (UCA), SonoVue (Bracco SpA, Milan, Italy) in rabbit liver VX2 tumor. METHODS: Liver VX2 tumor models were established in 20 rabbits, which were divided randomly into PHIFU combined with ultrasound contrast agent group (PHIFU + UCA group) and sham group. the PHIFU + UCA group, 0.2 mL of SonoVue was injected intravenously into the tumor, followed by ultrasound exposure of I_ (SP) 5900 W / cm ~ 2. The rabbits were sacrificed one day after ultrasound exposure. Specimens of the exposed tumor tissues were obtained and observed pathologi- cally under light microscope and transmission electron microscope. the remaining tumor tissues were RESULTS: Before TTC staining, tumor tissues in both the sham and the PHIFU + UCA groups resembled gray fish meat. After TTC staining, the tumor tiss ues were uniformly stained red, with a clear boundary between tumor tissue and normal tissue. Histological examina- tion showed of tumor cell injury in PHIFU + UCA group, with cytoplasmic vacuoles of various sizes, chro- matin margination and karyopyknosis. Electron micro- scopic examination revealed tumor cell volume reduction, karyopyknosis, chromatin margination, intercellular space widening, the presence of high electron-density apoptotic bodies and vacuoles in cytoplasm. CONCLUSION: The non-thermal effects of PHIFU combined with UCA can be used to ablate rabbit liver VX2 tumors.