Based on the vehicle system dynamics theory, exponential decay type dynamic irregularity was simulated as the locomotive model external excitation by using MATLAB software. The influence of the amplitude of exponential decay type irregularity on wheel/rail dynamics was analyzed under different-speed operation by using SIMPACK multi-body dynamics simulation software. The results showed that the exponential decay type irregularity would worsen the three indexes which were axle lateral force, wheelset decreasing ratio, and lateral vibration acceleration; Axle lateral force and wheelset decreasing ratio would diverge and converge at the same frequency and amplitude at the same time; And the three indexes would be even worse with the increase of irregularity amplitude or the increase of speed.