Dimethyl ether (DME) attracts increasing attentions in recent years, because it can reduce the carbon monoxide (CO), unburned hydrocarbon (HC), and soot emissions for engines as the transportation fuel or the fuel additive. In this paper, a reduced DME oxidation mechanism is developed using the decoupling methodology. The rate constants of the fuel-related reactions are optimized using the non-dominated sorting genetic algorithm II (NSGA-II) to reproduce the ignition delay times in shock tubes and major species concentrations in jet-stirred reactors (JSR) over low-to-high temperatures. In NSGA-II, the range of the rate constants was considered to ensure the reliability of the optimized mechanism. Moreover, an improved objective function was proposed to maintain the faithfulness of the optimized mechanism to the original reaction mechanism, and a new method was presented to determine the optimal solution from the Pareto front. The final reduced mechanism includes 42 species and 171 reactions. The comparisons between the measured and predicted results demonstrate that the present mechanism is capable of reproducing the ignition delay time in shock tubes and rapid compression machines, major species concentration in JSRs, flow reactors, and laminar premixed flames, as well as the laminar flame speed over the temperature range of 500-1500 K, the pressure range of 0.05-40 atm, and the equivalence ratio range of 0.25-2.0. Due to its compact size, the final mechanism is also coupled with the multi-dimensional computational fluid dynamic (CFD) to simulate the combustion and autoignition characteristics of DME in practical engines.