Hollow hydroxyapatite microspheres (H-HAMs) with controlled characteristic mesoporous structure on the shell were successfully fabricated by using core template technology and sol-gel process. The fabrication of H-HAMs mainly included three distinct steps: the preparation of core template spheres of chitin by emulsifying chitin solution in oil, the formation of core-shell composite spheres of chitin-HA/chitin after a layer of chitin/HA solution coated on the surface of chitin core templates by means of a gelling process of chitin solution with the help of water in the cores, and the harvest of H-HAMs through a special sintering procedure to remove chitin. The size and shape of H-HAMs were chiefly determined by the size and morphology of core templates. The thickness of shells was easily controlled by altering water content of the starting template particles, and the characteristic mesoporous structure on the shell was related to the proportion of chitin in the chitin/HA composite solution and the sintering temperature. H-HAMs with characteristic mesoporous architecture on the shell have many potential applications such as used as a carrier for sustained release of drugs in the therapy of hard tissue system.