In order to reduce the fuselage vibration amplitude of high-speed press, a transmission mechanism optimization method based on artificial bee colony algorithm was proposed. Then, the configuration of the transmission mechanism was introduced, and three-degree of freedom vibration model for fuselage was built. Next, the exciting loads and dynamic response of fuselage were solved, and the optimization model of transmission mechanism based on the fuselage dynamic response was built. Furthermore, the fuselage parameters were optimized and the value ranges of parameters were determined, the nectar source coding method and nectar source evaluation method were ingeniously set to transform the optimal parameter solving problem into the optimal nectar source problem of bee colony searching, and the optimal parameter combination was solved by artificial bee colony algorithm. After verification, the vibration amplitude of optimized fuselage in the X-axis direction is reduced by 24.68%, the vibration amplitude in the Y-axis direction is reduced by 66.67%, the vibration amplitude in the torsion direction is reduced by 30.13%, and the comprehensive objective function is reduced by 31.82%, indicating that the fuselage vibration amplitude in three-degree of freedom reduces greatly through parameters optimization, which greatly improves the performance of high-speed press.