Non-focused ultrasound and high-intensity focused ultrasound (HIFU) devices induce lipolysis by generating acoustic cavitation and coagulation necrosis in targeted tissues. We aimed to investigate the morphometric characteristics of immediate tissue reactions induced by 2 MHz, 13-mm focused HIFU via two-dimensional ultrasound images and histologic evaluation of cadaveric skin from the abdomen and thigh. Acoustic fields of a 2 MHz, 38-mm HIFU transducer were characterized by reconstruction of the fields using acoustic intensity measurement. Additionally, abdominal and thigh tissues from a fresh cadaver were treated with a HIFU device for a single, two, and three pulses at the pulse energy of 130 J/cm2 and a penetration depth of 13 mm. Acoustic intensity measurement revealed characteristic focal zones of significant thermal injury at the depth of 38 mm. In both the abdomen and thigh tissue, round to oval ablative thermal injury zones (TIZs) were visualized in subcutaneous fat layers upon treatment with a single pulse of HIFU treatment. Two to three HIFU pulses generated larger and more remarkable ablative zones throughout subcutaneous fat layers. Finally, experimental treatment in a tumescent infiltration-like setting induced larger HIFU-induced TIZs of an oval or columnar shape, compared to non-tumescent settings. Although neither acoustic intensity measurement nor cadaveric tissue exactly reflects in vivo HIFU-induced reactions in human tissue, we believe that our data will help guide further in vivo studies in investigating the therapeutic efficacy and safety of HIFU-induced lipolysis.