Quantitative ultrasound (QUS) techniques have been used for tissue characterization by discriminating between tissues of differing microstructure. High Intensity Focused Ultrasound (HIFU) is a means for minimal or non-invasive therapy, which results in changes in tissue microstructure. However, significant challenges remain for the monitoring and assessment of HIFU therapy. Conventional B-mode imaging is not reliable for detection and assessment of thermal lesions produced by HIFU. Because of QUS sensitivity to microstructure changes, it was hypothesized that QUS could assess thermal lesions. A 1-MHz single-element focused transducer (f/1.1) was used to produce thermal lesions in ex-vivo rat liver. The focal intensities used to generate lesions were measured to be between 1500 and 2500 W/cm2 in degassed water using a calibrated needle hydrophone. These exposures were monitored using a clinical ultrasound array (L14-5, Ultrasonix). Treated and untreated regions as determined by histology and visual inspection were compared to parametric images of QUS parameters (Effective Scatterer Diameter (ESD), and Effective Acoustic Concentration (EAC)). An average increase in ESD of 15% was observed in three samples, while EAC estimates decreased by 4.3 dB. These findings suggest that QUS can be used for non-invasive assessment of thermal lesions.