Preclinical mouse models are essential to the study of liver metastasis, yet their utility has been limited by difficulty in tracking the progression of metastases through time. In this study, liver metastases were identified by in vivo bioluminescence system and a high-frequency ultrasound system with nanobubbles. Tumor grows and vessel densities were calculated. Liver metastases were observed on the second days after inoculation and confirmed by the HE staining. Vessels density in the liver metastasis group was increased compared to the control group. This study show that three-dimensional high-frequency ultrasound imaging combined with nanobubbles may be suited for early detection, quantitative assessment of metastatic progression in liver metastasis models.