Myopia alters the collagen microstructure of the sclera which changes the tissue biomechanical properties. Although most forms of myopia are mild, progression of the disease to high or pathologic myopia can lead to significant weakening of the sclera and greatly increase the risk for the formation of a posterior staphyloma, a sight-threatening condition. Potential treatments to counteract effects of myopia on the sclera include chemical crosslinking (CXL). Formaldehyde releasing agents like sodium hydroxymethylglycinate (SHMG) are an attractive option for the posterior sclera because they increase tissue stiffness and require no light activation. Previous research has demonstrated that high-frequency quantitative ultrasound (QUS) is sensitive to the microstructural changes in the sclera caused by myopia. In this study, we investigate the ability of QUS to monitor microstructural changes caused by CXL. Ex vivo pig eyes were immersed in a 26.5 mM SHMG solution and scanned by an 80MHz ultrasound transducer at regular time intervals. RF echo data were analyzed to compute QUS parameters from the backscatter coefficient, normalized power spectrum, and echo envelope statistics. Correlations between QUS parameters and immersion time were investigated to evaluate the efficacy of QUS for monitoring CXL treatment. Results of this study demonstrate the capability to high-frequency QUS to assess changes in tissue microstructure caused by CXL with SHMG.