Abstract Targeted ultrasound contrast agents (UCAs) offer new opportunities to enhance the capabilities of diagnostic ultrasound imaging to detect pathological tissue. Poly (d, l-lactic-co-glycolic acid) (PLGA) UCAs based on microbubbles (MBs) were developed to target inflamed plaque, to aid in the diagnosis of atherosclerosis. A conjugation strategy was adopted using PLGA shelled MBs to enable localized targeting on atherosclerotic plaque by modifying the surface of these polymeric MBs with anti-ICAM-1. In addition, several investigations were carried out to determine the morphology and performance of the prepared MBs, including surface morphology, size distribution and conjugation efficiency analysis. Fluorescence microscopy and flow cytometry analysis showed a specific adhesion and high conjugation efficiency of targeting ligands to MBs. Furthermore, the conjugated MBs were applied in vivo ultrasound targeted imaging and the results demonstrated the availability of conjugated MBs as a highly efficient ultrasound system in targeted ultrasound imaging and in noninvasive biological research.