This article examines lesion formation using focused ultrasound and demonstrates how blood flow may affect lesion dimensions using a theoretical model. The effects of blood flow on temperature distributions during ultrasonic lesioning are examined for both regional cooling by the microvasculature and localized cooling due to thermally significant vessels. Regional cooling was critically assessed using two models: the Pennes bioheat transfer equation and the scalar effective thermal conductivity equation. Localized cooling was modeled by adding an advective term in the heat diffusion equation in regions enclosed by thermally significant vessels. A finite difference approach was used to solve the basic equations of heat transfer in perfused tissues in cylindrical coordinates. The extent of the lesioned tissue was determined by the accumulated thermal dose at each location. The size of the lesion was then calculated from the boundaries of the thermal isodose curves generated by the simulations. The results were compared to published in vivo lesion data in rat liver. It was shown that even for short ultrasound exposure times (approximately 8 s), blood flow may play an important role in the thermal dose distribution.