-thalassemia is an inherited hematological disease caused by a decrease or absence of production of -globin that requires chronic therapeutic interventions. This condition leads to important arterial and venous thromboembolic events, transitory ischemic attacks and microcirculatory obstructions, indicative of circulatory disturbances. To investigate the presence of microcirculatory disorders without the confounding effect of treatments, we used -thalassemic mice with typical clinical characteristics of human -thalassemia major. One impediment to the understanding of microcirculatory physiology, in particular for -thalassemic mice, has been the lack of an appropriate non-invasive imaging approach. We thus developed a novel non-invasive high-frequency ultrasound imaging method to evaluate murine vascular hemodynamic properties. In our -thalassemic mice, total peripheral vascular resistance was significantly increased (p < 0.01) compared to wildtype littermates, whereas mean blood pressure, heart rate and cardiac output were similar (p = non significant). Importantly, the vascular hemodynamics in -thalassemic mice was significantly affected according to the Pourcelot indices measured in the common carotid artery and abdominal aorta (p < 0.01 and p < 0.05, respectively). Hence, our -thalassemia characterization of vascular hemodynamics by non-invasive ultrasonic approaches proves the existence and provides unique quantitative assessment of microcirculatory flow disturbances in those mice.