Imaging of macrophage trafficking can reveal important molecular, cellular, and functional characteristics of the host tissue and support the discovery of new biomarkers for improved diagnosis, prognosis, and treatment monitoring. Over the past years, macrophage imaging using different modalities has undergone significant development, however existing modalities offer suboptimal tradeoffs between depth of penetration, specificity, sensitivity, and resolution. Although US could potentially address this challenge, while also providing portable assessment (e.g., in an outpatient setting) at potentially lower costs, there is a paucity of investigations using ultrasound for macrophage imaging. The central hypothesis of this thesis is that labelling macrophages with microbubble contrast agents to augment their contrast, can enable imaging of macrophage trafficking with high sensitivity deep into tissues without compromising resolution. In this study, we showed that macrophages can be effectively labeled with microbubbles, identified ultrasound exposure settings where they can retain high echogenicity and viability without affecting their functionality and confirmed that they can produce a strong image contrast in vivo for an extended period of time. Finally, we were able to demonstrate that we can monitor the trafficking of intravenously administered microbubble labeled macrophages in breast tumor-bearing mice. This research, thus, provides a novel framework for macrophage imaging and tracking using ultrasound to support the discovery and clinical translation of new ultrasound methods and technology for macrophage-based diagnostics and therapy monitoring.