Quantitative ultrasound (QUS), utilizing the fundamental theory of wave propagation, has been more and more used in diagnosing bone health and characterizing bulk material and mechanical properties of bone. In this work, the overall objective is to determine that ultrasound attenuation calculated from a quantitative ultrasonic system has enough sensitivity to detect the elastic deformation of cortical bone during axial compressive loading and provide information for calculating the mechanical properties of cortical bone. The ability of non-invasively access the mechanical properties of bone has many implications, such as diagnosis for stress fracture and osteoporosis. To test this methodology, this study began by investigating relation between ultrasound attenuation and cortical bone thickness in a simple bone plate numerical simulation model. The periodic results from the numerical simulation were then validated in computational simulation models of cortical bone plate and bone cylinder. The significant correlation between the results of numerical and computational models (R² = 0.51, P < 0.05) was then further validated in a in vitro cortical bone plate ultrasound testing. Result from the bone plate in vitro experiment provided consistent results with the numerical simulation, suggesting the ability of simulation in predicting the ultrasound attenuation in simple bone plate model. To test the feasibility of applying such method to true cortical bone, ultrasound measurement of ovine tibia cortical bone shell samples under quasi-static compressive loading was performed. The ultrasound device provided results with high linearity (R² = 0.922±0.044 in anterior-posterior direction, R² = 0.952±0.04 in medial-lateral direction) but of both positive and negative correlations with the loading displacement. The unexpected variability in correlations could be due to complex ultrasonic propagation pathways and signal interference. To explain such phenomenon, a plastic cylinder phantom was used to study the ultrasound attenuation in different propagation pathway. The high correlated results suggested the circumferential wave (CW) and direct wave (DW) showed opposite attenuation correlation with the mechanical loading. Such interference of ultrasonic waves from different pathways is expected to be more complex in true bone samples with irregular geometry and causing the variability of correlation between ultrasound attenuation and loading. Details of change in individual ultrasonic pathway should be taken into the consideration of the future work.