Previous studies of the biocompatibility of b-tricalcium phosphate (b-TCP) focused on bulk-sized b-TCP, and little is known about the biocompatibility of nano b-TCP particles (nb-TCP). The objectives of this study were to synthesize nb-TCP particles and determine their efficacy in a rabbit tibial defect model. The nb-TCP particles were first synthesized using a wet chemical precipitation process. The particles were then implanted in the left tibia of New Zealand white rabbits, and the defect site healing was evaluated for a period of 16 weeks using radiography, computed tomography, and histology. Data were compared with those of a sham (empty) control. Results showed that the defect site treated with nb-TCP particles did not heal completely after 16 weeks, whereas full cortical bone recovery was observed in the sham control group of rabbits. Histopathological examination showed that the nb-TCP particles caused an excessive and prolonged inflammatory response by the host. The nano-scaled size and biodegradability of the synthesized nb-TCP particles may have been responsible for this progressive and extended inflammatory response, which delayed the bone healing process. The underlying mechanism for this effect remains unclear and warrants further investigation.