Abstract Though the enhancement of barrier properties in flake-filled membranes is well known, its dependence on microstructural factors such as size dispersion, spatial distribution and orientation of the flakes is not well understood. This paper presents a direct numerical approach to modeling the diffusion in flake-filled membranes, and investigates the effect of fiber placement, misorientation and concentration on the effective barrier properties. Numerical computations were conducted in doubly-periodic two-dimensional unit cells containing up to 50000 individual randomly distributed flakes, which are either perfectly oriented in a direction or exhibit a randomly distributed misorientation by an angle (e) scatter in orientation around , perfectly oriented or disoriented flakes representative of the states in the dilute, semi-dilute and concentrated regimes. The results are analyzed and two new models are proposed. We also show that there are significant discrepancies between computational results and theoretical literature models when the fibers are not perfectly aligned perpendicular to the diffusion direction. Finally, we show the importance of using not only periodic geometries but also periodic conditions when estimating average field quantities.