The mechanism of cross-flow microfiltration of submicron microbes is studied. Experiments are carried out using pseudomonas suspensions. The effects of operating conditions on the filtration performance are discussed. The results show that the filtration rates increase with increasing the cross-flow velocity, while decrease with increasing the filtration pressure. The Brownian dynamic simulation method is adopted for simulating the trajectories of microbes in cross-flow microfiltration. The deposition flux of microbes on the membrane surface can then be estimated from the simulated trajectories. Based on the continuity equation of cake compression and Kozeny equation, a dynamic analysis method is developed for simulating the distributions of local cake properties, such as porosity and specific filtration resistance in the filter cake. The deformation of microbes, the area contact between microbes and the creeping effect of cake compression are taken into consideration. The simulated values of average cake properties agree with the experimental data. It can be found that a skin layer controlled the filtration rate will form next to the membrane surface. Although the thickness of the skin layer is only about 10% of the whole cake, it plays the major role on the filtration resistance. Increasing the filtration pressure results in more compact skin layer; therefore, a lower filtration rate is obtained. Moreover, a higher cross-flow velocity will results in a thinner but more compact cake, a higher filtration rate can be given.