We developed a novel localized antivascular method, namely photo-mediated ultrasound therapy (PUT), by applying synchronized laser and ultrasound pulses. PUT relies on high optical contrast among biological tissues. Taking advantage of the high optical absorption of hemoglobin, PUT can selectively target microvessels without causing unwanted damages to the surrounding tissue. Moreover, PUT working at different optical wavelengths can selectively treat veins or arteries by utilizing the contrast in the optical spectra between deoxy- and oxy-hemoglobin. Through our experiments, we demonstrated that cavitation might have played a key role in PUT. The addition of a laser pulse to an existing ultrasound field can significantly improve the likelihood of inertial cavitation, which can induce microvessel damage through its mechanical effect. In comparison with conventional laser therapies, such as photothermolysis and photocoagulation, the laser energy level needed in PUT is significantly lower. When a nanosecond laser was used, our in vivo experiments showed that the needed laser fluence was in the range of 4 to 40 mJ/cm2.