The purpose of this work was to investigate the effect of the chemical structure of various drugs on the exchange reaction kinetics and the release kinetics of calcium channel blockers such as verapamil hydrochloride (VH), diltiazem hydrochloride (DH).It was found that the exchange rates and equilibrium constants of exchange reaction increased with increasing of temperatures. The exchange reaction rate and apparent equilibrium constant of DH with low molecular weight and simple chemical structure were greater than that of VH with high molecular weight and complex chemical structure. The drug release studies in vitro showed that there was no found of VH and DH releasing from resinate when the deionic water was the release medium. The release rate increased with increasing of ionic strength of solutions, which indicates that the release of VH and DH from resinate strongly depends on the ionic strength of the release media. The diffusion of VH and DH within resin particles was controlled by particle diffusion process based on the equations of Body and Viswanathan. The diffusion coefficients increase with increasing of ionic strength of the releasing media. The release kinetics of VH and DH could be described satisfactorily by the equations of Boyd and Viswanathan. The results obtained in this study demonstrates that the exchange reaction process and the release process depend on the chemical structure and the molecular weight of the drugs as well as the cate ry of the counter-ions.