Solute transport through soft gels and tissues is intimately coupled to mechanical stress and deformation of the macromolecular network. The aim of this study was to investigate the effect of periodic mechanical stimuli upon solute transport through agarose gels at different concentrations. For this purpose it was experimentally evaluated the materials parameters that govern the coupling between elasto-dynamic and solute transport: hydraulic conductivity (K), elastic modulus (HA), and macromolecular diffusivity (Dg) along with their strain dependence behavior. Mechanical activated solute transport simulation was carried out in order to elucidate the role of amplitude and frequency of soliciting mechanical stimuli on mass kinetics release. Results show that mechanical loading affects the release of macromolecules from a gel in a frequency and strain dependent manner. These findings pave the way for novel strategies for the design and engineering of smart drug delivery devices with transport mechanisms triggered by mechanical stimuli. © 2008 American Institute of Chemical Engineers AIChE J, 2008