The objective of the present study was to synthesis of alkyl succinate and phthalate derivative of chitosan by substitution of neucliophilic amino group in order to modify the solubility window of the polymers. The synthesize derivatives were used in preparation of metronidazole (MN) and were investigated the efficacy for pH sensitive colon targeted drug release. The chitosan derivatives microspheres containing MN were prepared using solvent evaporation method. Formulations were characterized for morphology, particle size, % encapsulation efficiency, % drug content and in vitro drug release. The microspheres prepared by N-ethylsuccinate chitosan (batch F2) was found to be high drug encapsulation efficiency and was showed better stability in simulated gastric fluid. The drug release from this batch was 73±1.4 % (phosphate buffer) whereas in simulated gastric fluid was found 26±1.6% for 2 hr of the study. The mucoadhestion of the batch was found 75±1.5 % whereas, in plain chitosan microparticles was found 56±1.2 %. The result provides evidence that the prepared formulation of batch may be used effectively for pH sensitive colon targeted drug such as metronidazol.