The ultra-high acceleration macro and micro motion platform has the advantages of high positioning accuracy and small error, and the key mechanism rail frame of the ultra-high acceleration macro and micro motion platform is optimized based on modal analysis to achieve the performance optimization of the platform. SolidWorks software was used to build the rail frame model, and ANSYS Workbench software was used to carry out modal analysis, topology optimization and response surface optimization, etc., so as to reduce the quality of the rail frame as much as possible under the premise of maintaining the stability of the first-order natural frequency. The results show that the optimization of the response surface meets the expected goal, the first-order natural frequency of the guide rail frame increases by 0.7 %, the mass decreases from 6.165 kg to 5.592 kg, and the change rate is 9.2 %, which achieves the purpose of lightweight.