Low-intensity focused ultrasound was applied with microbubbles (Definity, Lantheus Medical Imaging, North Billerica, MA, USA; 0.02 mL/kg) to produce brain lesions in 50 rats at 558 kHz. Burst sonications (burst length: 10 ms; pulse repetition frequency: 1 Hz; total exposure: 5 min; acoustic power: 0.47-1.3 W) generated ischemic or hemorrhagic lesions at the focal volume revealed by both magnetic resonance imaging and histology. Shorter burst time (2 ms) or shorter sonication time (1 min) reduced the probability of lesion production. Longer pulses (200 ms, 500 ms and continuous wave) caused significant near-field damage. Using microbubbles with focused ultrasound significantly reduced acoustic power levels and, therefore, avoided skull heating issues and potentially can extend the treatable volume of transcranial focused ultrasound to brain tissues close to the skull.