How to diagnose the bone fatigue damage at early stages is one of the hot research subjects in bone evaluation field. In this study, the propagation characteristics of ultrasonic guide wave in a long bone under different elastic moduli are analyzed using theoretical calculation and simulation methods. First, theoretical solutions of guided wave in a long bone are calculated. Then, a finite difference time-domain (FDTD) numerical method of simulating the propagation of guide wave in a long bone is presented. The simulation results are in good agreement with the theoretical values. And, the relationship between elastic modulus and the propagation characteristics, including group velocity, central frequency and attenuation, is discussed. The results show that group velocity and central frequency increase with the increase of elastic modulus. However, attenuation decreases with the increase of elastic modulus. Those results demonstrate that the propagation of guide wave can reflect the variation of elastic modulus of long bone, which provides a theoretical basis for evaluating the early stages of fatigue damage in long bone.