The aim of the present study was to explore the therapeutic effect of 20 kHz ultrasound (US) and microbubbles (MBs) on rabbit VX2 liver tumors by spiral computed tomography (CT) scanning. A total of 16 New Zealand rabbits with hepatic VX2 tumors were divided into four groups: Control, MB, low-frequency US and US + MB. The treatment effect was evaluated by spiral CT scanning prior to, during and following treatment (at 0 weeks and the end of 1 and 2 weeks). The tumor growth rate was recorded. The specimens of VX2 tumors were collected for histological examination and transmission electron microscopy (TEM). No significant differences were observed between tumor areas measured by CT and pathology after 2-week treatment (P>0.05). The mean tumor growth rates in the control, MB, US and US + MB groups after 2 weeks of treatment were 385±21, 353±12, 302±14 and 154±9%, respectively (P<0.05, US + MB vs. the other three groups). Hematoxylin and eosin staining in the US + MB group revealed coagulation necrosis, interstitial hemorrhage and intravascular thrombosis. In the control, MB and US groups, tumor cells exhibited clear nuclear hyperchromatism. TEM of US + MB revealed vascular endothelial cell wall rupture, widened endothelial cell gaps, interstitial erythrocyte leakage and microvascular thrombosis, while intact vascular endothelial cells and normal erythrocytes in the tumor vessels were observed in the control, MB and US groups. A combination of 20 kHz US and MBs may effectively inhibit rabbit VX2 tumors. Spiral CT scanning is an ideal method to evaluate the US treatment on rabbit tumors.