Some ion exchange resins like Cholestyramine (Duolite AP-143), provide extended gastric retention and have the ability to coat the gastric mucosa uniformly. The use of such mucoadhesive ion exchange resins is another attractive approach in the development of targeted formulations for the GIT. In pesent work, a mucoadhesive gastroretentive system for Repaglinide was developed and optimized using Duolite AP-143 resin by RSM. Studies were carried out to develop and optimize oral mucoadhesive beads for Repaglinide using ion exchange resin and chitosan. Resinates prepared were studied for the effect of pH and drug resin ratio on drug loading. Resin and resinates were evaluated for mucoadhesive property using falling liquid film method. Resin and resinates showed sufficient mucoadhesion strength when compared with other mucoadhesive polymers and other ion exchange resins. Dissolution study of Repaglinide resinate showed that Duolite AP-143 was able to sustain the release of drug. The study suggests that the mucoadhesive beads of Repaglinide provide sustained release over 8 h and also shows sufficient mucoadhesive strength with rabbit gastric mucosa.