It is well known that the targeted fuel efficiency could only be achieved by more than 40% reduction of the vehicle weight through improved design and extensive utilization of lightweight materials. In order to obtain the goal of the weight reduction of automobiles, the researches about lighter and stronger rear sub-frame have been studied without sacrificing the safety of rear sub-frame. In this study, the weight reduction design process of rear sub-frame could be proposed based on the variation of von-Mises stress contour by substituting an AA6061 (aluminum 6061 alloy) having tensile strength of 310 MPa grade instead of SAPH440 steels. In addition, the stress ratio variations (stress over fatigue limit) of the rear sub-frame were examined and compared carefully. It could be reached that this approach method could be well established and be contributed for light-weight design guide and the optimum design conditions of the automotive rear sub-frame development.