The preparation of a potential prolonged-release matrix tablets (IER-tablets) containing diclofenac sodium – anion exchange resin (Dowex I-X8.Cl-) complexes has been performed by direct compression of the drug-resin complex (drug resinate) with various release-regulating excipients (Avicel PH 101, lactose, sodium carboxymethylcellulose, and compritol). All the formulations produced tablets with good mechanical properties. The in-vitro release rate of diclofenac sodium from the drug-resin complex samples with different loaded concentrations and from the prepared IER-tablets (Kh = 0.92-5.52 mg/min-0.5) was determined using a rotating paddle dissolution apparatus. The results obtained showed that drug release from these formulations was slower than from the tabletted diclofenac sodium alone (Kh = 6.55-15.10 mg.min-0.5) or a commercial sustained-release tablet formulation of diclofenac sodium (Kh = 8.23 mg.min-0.5) and that IER-tablets containing sodium carboxymethylcellulose or compritol exhibited the lowest release rates (Kh = 0.92 and 1.27 mg/min-0.5, respectively). The kinetics of the drug release from resinate was evaluated on the basis of the mass low. In most cases, the profiles for both the effect of drug/resin ratio and sodium ion concentration upon drug release from the resonates exhibited two release rate processes: rapid release during the initial period, followed by a decreasing release rate, suggesting a particle diffusion release process. The release rate data of the tablets were investigated by using zero-order and the matrix-diffusion-controlled kinetics. The calculated exponential release exponents (n-values) revealed that release behaviour of all IER-tablets was a Fickian-diffusion kinetics (i.e., The Higuchi-linear square root of time relationship), confirming that a matrix diffusion-controlled mechanism was operative. To evaluate the feasibility of the drug resinate tablet system, the optimum IER-tablet formulations, drug resonates, sustained-release commercial tablet product and plain drug were examined for their ulcerogenic activity in rabbits. The results proved the superiority of the drug resinate and IER-tablets containing Avicel PH 101 over the plain drug, commercial product or IER-tablets containing compritol or sodium carboxymethylcellulose. Overall, this study demonstrated the significance of using ionic complex systems in offering a simple gastro-protected tablets and showed the characteristics of the matrix materials and their influence on the drug activity as well as tablet performance in-vivo.