Oral colon-targeted microsphere based drug delivery system containing sulfasalazine was prepared, optimized and characterized. The microspheres were successfully prepared by simple emulsification phase-separation technique followed by crosslinking. The formulations were optimized on the basis of drug: polymer ratio, stirring speed, concentration of glutraldehyde. The prepared microspheres were characterized on the basis of morphology, entrapment efficiency,particle size and in-vitro release.