The aim of this work was to analyse the hindrance effect of the naturally derived bioactive polymer hyaluronic acid (HA) considered responsible for the interstitium transport regulation. The diffusion coefficient measurements of several macromolecular probes, different for nature and dimension have been performed within HA water solution and HA collagenous gels in order to study the role of HA on the control of macromolecular transport. HA matrices showed less diffusional hindrance then HA water solutions. Moreover, the HA, interpenetrating with the collagen fibres, selectively affected the transport, depending on the HA concentration. These preliminary studies indicate that the biopolymer HA can be employed to design novel biopolymer interpenetrating gels suitable as molecular sieves for membrane permeation and controlled drug delivery. (c) 2005 Elsevier B.V. All rights reserved.