A multiparticulate system combining pH sensitive property and specific biodegradability has been investigated to prepare and evaluate ES-100 coated chitosan microspheres for colon targeting of ibuprofen. Chitosan microspheres were prepared by emulsion cross-linking method using different ratios of ibuprofen and chitosan (1:1, 1:1.5, 1:2 ), at emulsifier concentrations of 0.5%, 0.75%, 1% w/v and cross linking agent at concentrations of 8, 9, and 10 ml. Eudragit coating of ibuprofen chitosan microspheres was performed by coacervation phase separation technique with different core: coat ratio of 1:4 and 1:5. Chitosan microspheres and eudragit coated chitosan microspheres were evaluated for surface morphology, particle size measurement and size distribution, percentage drug entrapment and in vitro drug release in simulated gastrointestinal fluid. The size of the core microspheres ranged from 90 to 130 μm and that of coated microspheres ranged from 130 to 165 μm. The core microspheres sustained the release for 8 hrs in a pH progression medium mimicking the condition of gastro intestinal tract. The release studies of coated microspheres were performed in a similar dissolution medium as mentioned above. In acidic medium the release rate was much slower, however, the drug was released faster at pH 7.4 and the release was sustained up to 24 hrs. There was no significant change in the particulate shape and drug content after storage at 5o ± 2oC/Ambient, 25 ± 2oC/ 60% RH and 40 ± 2oC/ 75 % RH for a period of 6 months. It is concluded from the present investigation that eudragit coated chitosan microspheres serve as promising controlled release carriers for colon-targeted delivery of ibuprofen.