Histotripsy uses high-intensity focused ultrasound pulses at low duty cycle to generate energetic bubble clouds inside tissue to fractionate a region. As a potential tumor treatment modality, this cavitation-based non-invasive technique has the advantages of easy monitoring and sharp borders. Aiming at therapy efficiency, we experimentally investigated the effects of pulse repetition frequency (PRF) and lateral scan step size on the dimensions of lesions formed through HIFU histotripsy in agar mimicking tissue in terms of mechanical (not acoustical) properties. The single-element spherically focused source (1.1 MHz, 6.34 cm focal length, f/1) was excited to reach the peak compressional and rarefactional pressures of ~102 and 17 MPa, respectively. A targeted rectangular block of 4.5 mm wide (lateral) and 6mm deep (axial) was scanned in a raster pattern with a constant axial step size of 3mm. The lateral step size was varied between 375, 750, 1500, 2250 and 4500 μm. Pulses at each treatment location consisted of 5000 20-cycle sine wave tone bursts with the PRF of 167, 333 or 1000 Hz. Results suggested that the bubble activity region could extend beyond the -3 dB region and that refining the lateral scan mesh and/or increasing PRF enlarged the lesion extent. The 1500 μm-333 Hz and the 1500 μm-1 kHz conditions were in a more favorable position to be viewed as optimal with regard to lesion volume generation rate, bubble activity region width, and the potential for thermal damage.