A mathematical model for internal fouling in protein microfiltration is developed to correlate flux decline and protein transmission with protein adsorption on pore surface during filtration. The model was constructed based on the mass balance of protein in a small section of membrane assuming that multilayer adsorption occurs in the pore, which consists of primary adsorption of proteins on the clean surface and the secondary one on the adsorbed protein. The flux decline is evaluated by a pore narrowing model which considers protein adsorption, The previously reported experimental curves of flux decline and protein transmission rate are fairly well simulated by this model using six fitting parameters, which are adsorption capacity, adsorption coefficient, and thickness of adsorption layer, in both the primary adsorption and the secondary adsorption.