As a novel drug delivery approach, piroxicam an anti rheumatoid drug is loaded in microspheres prepared by chitosan as a polymer and coated with eudragit S-100 to prepare colon speci c microspheres which increases the bioavailability of the drug to the targeted area and in a controlled manner and reduces GI related side effects. In the present study chitosan microspheres were prepared using emulsion crosslinking technique, glutaraldehyde as a crosslinker and microencapsulation using phase coacervation technique. Optimization is done by varying drug- polymer ratio (1:2 to 1:8), emulsi er concentration, i.e., span 80 (0.5 ml, 0.75 ml, 1 ml), stirring speed (500 rpm, 1000 rpm, 1500 rpm, 2000 rpm, 2500 rpm), cross-linker concentration (2.5 ml, 5 ml, 10 ml) and coat-core ratio from 1:2 to 1:6. The prepared chitosan microspheres showed high entrapment ef ciency about 97.29% with percent yield 90.26. In the present study FTIR studies con rmed the absence of interactions between the pure drug, i.e., piroxicam and the excipients used. SEM images revealed that the prepared chitosan microspheres were spherical in shape with rough surface and particle size ranged from 90.21 to 172 μm. Showed good drug release pro le for both coated and uncoated chitosan piroxicam microspheres of about 86% and 96%. Drug release kinetics showed that microspheres followed korsemeyer peppas model indicating the drug diffusion mechanism from polymer matrix.