Deflection is one of the main injection molding defects which must be minimized to improve the quality of an injection molding product. In particular, the thickness of the injection molding part is a major factor affecting the deflection of the product. In this study, unit grid thickness distribution of a model mesh is determined as the design variables exploiting the symmetry of a rectangular plate, in order to minimize both the deflection and mass of the injection molding part. Since the optimization problem with many design variables requires a lot of iterations of analysis, a commercial process integration and design optimization (PIDO) software, PIAnO 2017, is employed for efficient optimization procedure. The PIAnO provides orthogonal array tables for design as well as a capability of file parsing, which helps to automate the Moldflow analysis procedure. Also, the causes of the deflection are analyzed by comparing the thickness distribution pattern of different resin materials.