The ultra-high acceleration macro-micro motion platform has the advantages of high positioning accuracy and small error. Based on the modal analysis,the guide rail frame of the key mechanism of the ultra-high acceleration macro-micro motion platform was optimized to optimize the performance of the platform.SolidWorks software was used to build the guide rail frame model,modal analysis,topology optimization and response surface optimization were performed by ANSYS Workbench software,to reduce the quality of the guide rail frame as much as possible while maintaining the stability of the first-order natural frequency.The results show that the response surface optimization is line with the expected target,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 light weight.