Purpose To prepare the tranexamic acid liposome with high encapsulation efficiency and stability, through interaction of avidin and biotin, and to prepare its microbubble-liposome compound whose properties are to be assessed. Materials and Methods Thin film hydration technology was used to prepare tranexamic acid liposome. Taking encapsulation efficiency as indication, the microbubble-liposome compound was optimized by the design of orthogonal experiment. The basic properties of the compound were tested and the acoustic characteristic was measured by ultrasound and gray-scale values. Results The optimum formula of tranexamic acid liposome were as follows:molar ratio of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[biotinyl (polyethylene glycol) 2000] was 85∶10∶5;concentration of tranexamic acid was 5.0%;ultrasonic time was 15 min. The encapsulation efficiency was 62.62%. The size was approximately (104.00±1.84) nm. The Zeta potential was approximately (-50.50±0.56) mV. The liposome was good in stability. The size of the microbubble-liposome compound was approximately (4.56±0.28)μm. Under the microscope, they were round with transparent center, evenly distributed without aggregation. The acoustic characteristic of the compound in vitro showed typical characteristics of microbubble, which was compatible with the results under the microscope. As the concentrations of the compound increased, both ultrasound imaging effect and the gray-scale values enhanced. However, to avoid acoustic shadows, the imaging concentrations were supposed to be at least lower than 1.15×108/ml in vitro. Conclusion The preparation of the tranexamic acid microbubble-liposome compound can be optimized by taking encapsulation efficiency as reference, and it can be effectively traced by ultrasound according to its acoustic characteristics in vitro.