An aerodynamic optimization chain based on CFD is built for conceptual and preliminary design of unconventional aircraft layout. In this paper, the combination of NURBS parameterization method and CPACS (Common parametric aircraft configuration schema) data format developed by DLR can successfully describe the parameterized configuration of the entire aircraft. The grids for calculating the Euler equations are automatically generated and the aerodynamic characteristics of parameterized aerodynamic shape are evaluated. Then the response surface model (RSM) is built. Based on RSM the SQP gradient algorithm is sought under satisfying constraints. An OneraM6 wing is chosen to validate the optimization chain. The optimization results indicate that under conditions of constraint, he drag coefficient of the optimized wing is reduced severely .