The feasibility of Doppler tissue imaging (DTI) for assessing global systolic function has not been determined in small animals, particularly at near-conscious heart rates. Therefore, we compared DTI measurements with conventional M-mode-derived fractional shortening in murine global left ventricular systolic dysfunction induced by intraperitoneal doxorubicin (Dox) injection. In all, 13 female C57BL mice received 20 mg/kg of Dox and 12 mice received saline injection (controls). DTI signals were obtained from the inferior wall through parasternal short-axis views. The heart rate was kept at near-conscious level throughout DTI measurements (approximately 500/min). Left ventricular systolic dysfunction was detectable by measurements of fractional shortening from 4 to 14 days after Dox administration. Among DTI measurements, peak systolic velocity and time to peak systolic velocity decreased from 4 to 14 days after Dox injection. Our results indicate that these new DTI measurements appear feasible to assess global left ventricular systolic dysfunction in mice.