Dimethyl Ether (DME, CH3OCH3) is the simplest ether and considered as one of the leading candidates for the substitute of petroleum-based fuels. In this work, we analyzed one-step DME synthesis in a shell and rube type fixed bed reactor and carried out simulation with a one-dimensional, steady state model of heterogeneous catalyst bed with consideration of the heat and mass transfer between catalyst pellet and reactants gas and effectiveness factor of catalysts together with reactor cooling through reactor tube wall. We compared behaviours of the reactor using two different arrangements of catalysts, mixture of catalyst pellets and hybrid catalyst. The effects of several parameters including feed temperature, GHSV (Gas Hourly Space Velocity), H2 to CO ratio in the feed gas, reactor pressure and ratio of methanol synthesis catalyst to methanol dehydration catalyst were investigated. Results of the simulation indicate that hybrid catalyst is better than mixture of pellets in terms of CO conversion, DME yield and DME productivity due to proximity of active sites of two different catalysts.