A novel biodegradable graft co-polymer based on cellulose diacetate (CDA) and poly(p-dioxanone) was synthesized by ring-opening polymerization of p-dioxanone (PDO). The molecular structure of co-polymers was characterized by one- and two-dimensional NMR. The graft co-polymers with different lengths of PPDO side-chains could be controllably synthesized by changing the in-feed ratio of CDA/PDO. It was found that the PPDO content had great effect on the thermal transition behavior, crystallization ability and thermal stability of the graft co-polymer. The in vitro degradation rates of CDA-g-PPDO were higher than that of linear PPDO due to their lower crystallinity. Moreover, porous microspheres of graft co-polymers with a diameter of about 5 μm, prepared through the solvent evaporation of water-in-oil emulsion (W/O), indicated it may have potential applications in drug-delivery systems.