An Environmental Control and Life Support System (ECLSS) for a large manned spacecraft, such as the International Space Station, is mainly a regenerative ECLSS. Its system is very complex, so it is necessary to conduct on simulation research in order to optimize its design and operation conditions. In this type of simulation optimization work, the substance flow simulation, that is the pressure and flow simulation, is the base of the whole substance and energy simulation. Based on the characteristic analysis of substance flow in multiple subsystems of ECLSS, a typical characteristic system is abstracted from these real physical systems and the corresponding flow models are set up. In addition, two connect methods for flow nets are also presented in order to solve the flow models dynamically in the Matlab/Simulink environment. The simulation results show the feasibility of the above methods.