The interactions between membrane and particles or among particles were examined based on DLVO theory in order to probe complex membrane fouling phenomena. The strength of the interactions depends on the competition between van der Waals attraction and electrostatic double layer repulsion. An on-lattice Monte Carlo model was developed for two-dimensional membrane pore and surface to simulate pore blocking and cake formation. Effects of interactions on membrane retention, membrane resistance, and cake layer density were studied with the microstructural changes in cake layer formation. The model can be widely applied to the analysis of membrane fouling for a variety of foulants.