Recent development in structure optimization offers the potential for significant improvements in the design of more durable structures. The present paper reveals the importance of structural optimization with crack propagation life of integrally stiffened panels. In the full paper, we explain in detail how to optimize structural fatigue life and design the structure of integrally stiffened panels which has the optimization life. The first topic is: the review of existing structural optimization design method. The second topic is: optimization methodology with crack propagation life. In our optimization methodology, the RSM (Response Surface Methodology) and GA (Genetic Algorithm) are successfully applied for structural optimization design with crack propagation life. The third topic is: damage tolerance optimization of integrally stiffened panels with crack propagation life. In this paper, structural parameters: the height and location of stringer, are the design variables. The structural weight is a fixed value. Through analyzing, the optimization structure with maximum life can not simply be chosen, and the maximum life would not increase all ways while the high of stringer increased. At last, the optimization structure, which has maximum crack propagation life, is given on the integrally stiffened panels.