In this work, a spatial model of direct methanol fuel cell (DMFC) is built in Comsol Multiphysics and a system model is built in Matlab Simulink. The peripheral components such as the compressor for the air supply and the pump for the methanol supply are considered in this system model. The dynamic response of the system and the cell internal behavior to fluctuant loads is investigated by connecting the system model and the cell spatial model. During the simulation a series of signals are exchanged between these two models simultaneously such as the flow rate and temperature of the methanol and air, cell voltage, cell power and information about the exhausts. Furthermore, it can be also investigated the power consumption of the peripherals and the efficiency of the cell and system. At the end, the system regulation strategy for a better cell performance is investigated. Copyright (C) 2015, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.