Ultrasound imaging is widely used in the diagnosis of a variety of diseases due to its plenty of advantages, such as non-invasive, painless, real-time monitoring and low cost. However, some issues are with weak echoes. As a result, it is necessary to enhance the ability of ultrasound imaging by using an ultrasound contrast agent (microbubbles) with strong echo characteristics. At present, most of the microbubbles approved for clinical use consist of surfactants or phospholipids. Because of their strong compressibility, these bubbles can enhance the ultrasonic Doppler signal of blood flow and improve the clarity and resolution of ultrasonic images. But they still have some disadvantages, such as their limited stabilization effect and short blood circulation time, which limits the ability to inspect lesions that need long-term observation such as small lesions. Particle stabilized bubbles (PSBs) are bubbles formed by particles instead of surfactants stabilizing the gas-liquid interface. Compared with surfactant stabilized bubbles, the PSBs system has higher stability, because the particles are irreversibly adsorbed at the gas-liquid interface, which makes them a great potential ultrasound contrast agent. However, there are few studies on the preparation and application of particle-stabilized bubbles. The main reason is that the system requires a very narrow range of contact angles for particles. Once the range exceeds the defined range, the bubbles will burst rapidly. This work aims to prepare stable PSBs and to solve the problem of lacking research on PSBs at present. In this experiment, we did an extensive screening of different hydrophilic and hydrophobic particle stabilizers, then we investigated the influence of their charge, concentration, particle size, water phase and gas equal factors in forming PSBs. Finally, we prepared PSBs stabilized by chitosan nanoparticles (CNPs). On this basis, the biocompatibility of the system was evaluated by cytotoxicity test, hemolysis test and pathological section test. The contrast-enhanced performance of the system in vitro and in vivo was explored by a small animal ultrasound imager. These experimental results showed that CPSBs have good biocompatibility and imaging ability, indicating that the CPSBs system could be used as an ultrasonic contrast agent.