The recent advances in controlled delivery systems for protein pharmaceuticals such as microspheres, liposomes, pumps and implants, have provided a new avenue for delivery of vaccine antigens. Adjuvants aimed at increasing the immunogenicity of recombinant antigens remain a focus in vaccine development worldwide, there is currently considerable care for the development of chitosan microspheres as controlled release of vaccines, since the major disadvantage of several currently available vaccines is the need for repeated administration. Microspheres prepared from the biodegradable and biocompatible polymers, chitosan have been shown to be effective adjuvants for a number of antigens. This review mainly focuses on chitosan microspheres adjuvant as vaccine delivery systems by summarizing our and other research groups' investigation on properties of microspheres formulation encapsulating several kinds of antigens. The results indicate that compared with commonly used PLA and PLGA, chitosan biomaterial has several potentials in vaccine delivery systems. Chitosan microspheres can control the rate of release of entrapped antigens and therefore, offer generation adjuvant to replace or complement existing aluminium salts for vaccine potential. The review mainly aims to promote the investigation of chitosan microspheres adjuvant for antigens for world wide researcher.