BACKGROUND: Oxygen diffusion properties affect the proliferation and metabolism of cells cultured in microcapsules with a polyelectrolyte complex membrane. The effective diffusion coefficient (De) of oxygen in alginate/chitosan (AC) microcapsules under different preparation conditions was calculated, and a mathematic model was developed to investigate the effect of oxygen diffusion on cell loading in the microcapsules. RESULTS: Oxygen De in AC microcapsules was independent of alginate solution concentration, intrinsic viscosity of alginate and different polyelectrolyte complex membranes. De decreased from 2.1 +/- 0.3 x 109 to 0.17 +/- 0.01 x 109 m2 s1 as microcapsule diameter decreased from 1800 to 45 0 mu m. Microcapsule density was increased from 1.013 +/- 0.000 to 1.034 +/- 0.003 g mL1 as diameter decreased from 1775 to 430 mu m. The mathematic model results showed that critical CHO cell loadings were 1.8 x 108 or 1.1 x 108 cells mL1 in microcapsules with 450 or 1800 mu m diameter, respectively. CONCLUSIONS: No significant difference was found of oxygen De between calcium alginate beads and AC microcapsules. The decrease of De with diameter was attributed to the increasing density and compact degree on the surface. The model results indicated that risk on necrosis rose with the increasing diameter. Microcapsules with smaller diameters may have more advantages on cell culture. (c) 2012 Society of Chemical Industry