The lack of bone regenerative capacity of hydroxyapatite (HA)-based bone repair materials compared to allograft bone is due to a gap in angiogenesis and osteogenesis. Zinc oxide nanoparticles (ZnO NPs) release Zn2+ through their nanostructures to affect osteogenesis and angiogenesis, thereby improving the osteogenic activity. In this study, porous HA scaffold and porous ZnO/HA scaffold were prepared by spark plasma sintering without a binder. The microstructure and surface morphology of the scaffold were characterized by XRD and SEM. The biological safety and bone regeneration of the scaffold were evaluated by rabbit radial bone defect model. The porosity of scaffolds was greater than 40 % and the pore size range was between 50 and 500 mu m, which provided sufficient space for new bone tissue growth. The addition of ZnO nanoparticles did not affect the pore characteristics of the scaffold. After implantation in vivo, the results indicated that porous HA and ZnO/HA scaffolds presented good biocompatibility. The slow release of Zn2+ from ZnO NPs could inhibit the inflammatory response. The in vivo results of the radial defect model confirmed that the ZnO/HA scaffold had good bone regeneration ability. The ZnO NPs effectively improved the angiogenesis and osteogenesis of porous hydroxyapatite scaffold and promoted new tissue formation. This study reveals the effect of the addition of ZnO NPs on the physical and chemical properties and tissue regeneration of porous hydroxyapatite-based scaffolds, and provides a promising strategy for the design of hydroxyapatite-based scaffolds for clinical treatment of bone defects.