Application of non-pneumatic tire (NPT) has been increased during the last decade. The aerodynamic characteristics of the wheel with NPT has been studied due to significance on improvement of handling and reduction of fuel consumption. In this paper, first, an original NPT model was simulated by CATIA software, and the influence of NPT structural parameters on aerodynamic characteristics was studied by Fluent software. The simulation calculation results showed that: the reduction of tire width and spoke length, and the increase of spoke thickness can effectively decrease aerodynamic coefficient. Then, the MIRA model was used to study the influence of NPT on aerodynamic characteristics of the whole vehicle under driving conditions. Studies showed that: NPT increased the resistance of the whole vehicle, and 63.1% of the resistance at the wheels was provided by the front wheels. Finally, the wind tunnel test was conducted to study aerodynamic characteristics of the optimized NPT model under static conditions and verify the simulation calculation.