The use of microchannels in industrial-scale reactors requires a very large number of parallel microchannels. In order to maintain the performance of this multi-scale reactor, a uniform flow distribution must be ensured, while maintaining an acceptable pressure drop. This work presents a step-by-step methodology that enables to calculate the flow characteristics (maldistribution and flow resistance) of multi-scale microchannel reactors, under laminar and isothermal conditions. A successive assembling of two-scale networks is considered to build the entire multi-scale network. Thus, based on a resistive model and taking into account the self-similar topology of the network, this methodology simplifies the multi-scale network into a two-scale equivalent network, whose characteristics can be read on design charts. Combination of intermediate values obtained at each step of the method then enables to calculate the global characteristics of the entire network. Successive applications of this methodology on various network arrangements finally enable to discriminate them and choose the most-appropriate design.