Abstract: A systematic approach for predicting the hindrance factor of macromolecular diffusion in micropores is reported, simultaneously taking into account the molecular dimension and shape effects. The general theoretical fundamentals are described in term of the movement of a rigid spherical particle through a long circular cylindrical pore of comparable dimension. Modeled as one of six typical shapes, the shape effect of macromolecules is considered by defining a geometric characteristic radius to calculate the concentration partitioning coefficient and a hydrodynamic equivalent sphere radius to evaluate the hydrodynamic reverse drag coefficient, in substitution of the previously used Stokes -Einstein radius. The experimental tests for four macromolecules of typical shapes: dextrane, ficoll, polystyrene and bovine serum albumin, are carried out with the polycarbonate track-etched membranes. The quantitative comparison indicates that the results obtained from the theoretical calculation are consistent with the experimental data.