Cake layer formed on membrane surface presents a major challenge to membrane permeation, and it can be considered as a porous media. Determination of the cake layer permeability is critical for an accurate analysis and design of membrane filtration. A permeation model, based on fractal theory and Darcy's law, for evaluating cake layer permeability in microfiltration of activated sludge wastewater was developed. The cake layer permeability was derived and found to be a function of the pore-area fractal dimension and microstructural parameters. The validity of the model was studied systematically in this paper. The permeation model was applied to study the effect of mixed liquid suspended solids (MLSS) concentration, particle size distribution (PSD) and extracelluler polymeric substance (EPS) on cake layer permeability in a submerged membrane bioreactor. Results showed that the permeation model was a useful tool to study the micromechanism of membrane fouling. There was a close correlation between MLSS concentration and cake layer permeability. There were a slight and a distinct decrease of the cake layer permeation as MLSS increased less and larger than 10,000mg/L, respectively. PSD and EPS are two significant factors affecting cake layer permeability in membrane bioreactor. Effect of activated sludge on cake layer permeability was mainly caused by EPS and small particles attached on membrane surface.