Fuel economy is the key performance for the vehicle besides emission, which has been compulsory controlled by the legislation. For the electronic controlled Diesel engines, the mentioned properties could be satisfied not only by engine design but also by engine performance tuning. Fuel economy may be influenced by many coupled factors, such as injection timing, speed, load and under the limitation of cylinder peak pressure and exhaust temperature. To achieve a high efficient calibration, a model based calibration was performed on a four cylinder electronic unit pump Diesel engine with exhaust gas recirculation. The objective of the study is to solve the complexity of the interactions among the engine running parameters and the best fuel economy performance in order to meet under the restriction of NOx emission performance. The study was carried out in four stages. First, the experiment design has been proposed to identify designed experiment operating points and weighting factors. Second, two-stage statistical engine responses and boundary models have been established. Third, the global optimization and European steady-state cycle operating point optimization have been carried out. Finally, the bench test has been conducted on the Diesel engine. The global operating points results show that the fuel consumption rate has decreased at most test operating points by model based calibration. The fuel consumption rate has decreased by 3.5%, and 13 mode cycle test results indicate that the proposed model based calibration method is effective and can improve the fuel efficiency by 2.72% compared with the traditional calibration