A semi-analytic model to predict the permeate flux during high-pressure ultrafiltration of blood with highly permeable membranes is proposed. This model explicitly considers the hydraulic resistance of the retained particles that limits the flux. An empirically derived relationship between particle surface concentration and hydraulic resistance is used. This model incorporates the axial variations in blood cell and solute surface concentrations (or concentration polarization), shear-induced diffusion coefficient for the blood cells, effective diffusion coefficient for the blood solutes, hydraulic (lumen) pressure, and flow rate. This model agrees well with experimental results in the pressure-independent filtration flux region.