The role of the permeability barrier of the outer membrane of Pseudomonas was re-evaluated based on the physical theory of molecular sieving in view of its intrinsic antibiotic resistance. We developed a set of analytical procedures based on parametric and non-parametric statistical tests to evaluate, validate and adopt the better among a set of competing non-linear models of diffusion. The molecular mass dependence of uptake of non-electrolytes in bacteria yielded a quantitative measure to distinguish between sieving mechanisms and specific uptake/efflux mechanisms. The experimental data, supported by the physical model of DEAE-Sephadex and various analytical models and extensive simulation of the errors, both in measurement and models, yielded evidence consistent with the relaxation of the outer membrane matrix barrier in Pseudomonas.