Oral insulin administration is limited due to its degradation by proteases. The hormone was encapsulated in spheres made of either pure calcium alginate (ALG) or its association with whey protein isolate (WPI-ALG) in order to minimise loss in the stomach region while allowing liberation in the maximum absorption area, located in the intestine. Diffusion coefficients for both matrix compositions were determined in vitro for gastric pH (5.88 and 10.26 x 10(-12) m(2) s(-1)) and intestinal pH (21.11 and 79.29 x 10(-12) m(2) s(-1)). Higher initial insulin concentrations and lower diameters accelerated its release, confirming Fickian behaviour. The analytic model exhibited a good fit in most cases. Computer simulations revealed that ALG spheres are more convenient for oral administration because they release more insulin in the intestine than the WPI-ALG ones, thus supporting its therapeutic viability for the purpose of reducing stress in those who depend on insulin.