To develop a new generation of absorbable fracture fixation devices with enhanced biocompatibility, the biodegradation mechanism and its influence on the cellular response at the tissue/implant interface of hydroxyapatite/poly-DL-lactide (HA/PDLLA) composites were investigated in vitro and in vivo. HA/PDLLA rods were immersed in phosphate-buffered saline, or implanted in muscle and bony tissue for 52 weeks. Scanning electron microscopic and histological studies were done. The degradation rate was the slowest in vitro, slower in muscle tissue and fast in bone. In vitro, the composites degraded heterogeneously and a hollow structure was formed. In bone, the limited clearing capacity leads to the accumulation of oligomeric debris, which contribute totally to the autocatalytic effect. So, the fastest degradation and intense tissue response were seen. In muscle tissue, oligomeric debris migrated into vicinal fibers over a long distance from the original implant cavity and the tissue reactions were, however, quite moderate. For the same size organic/inorganic composite, the environment where it was placed is the major factor in determining its biodegradation process and cellular reaction. In living tissue, factors such as cells, enzymes and mechanical stress have an obvious influence on the biodegradation and biological process at the tissue/implant interface. The biocompatibility of the HA/PDLLA composites is enhanced with the incorporating of the resorbable HA microparticles.