The aim of this study was to assess the histocompatibility of hydroxyapatite (HA)/poly(lactic-co-glycolic acid) (PLGA)/bone morphogenetic protein-2 (BMP-2) composite materials in rabbits. Thirty healthy New Zealand white rabbits were randomly divided into 3 groups (N = 10). HA/PLGA/BMP-2 composite materials with the HA/PLGA proportions of 1:1, 1:2, and 1:3 were implanted in the animals, which were subsequently sacrificed on the 30th and 60th days post-implantation to allow for differences in routine blood and biochemical indices to be assessed between the animal groups. The degree of biomaterial degradation was also assessed in the three groups. Thirty and 60 days after the implantation of titanium plates and composite materials, no rabbits succumbed to inflammatory reactions, adverse reactions, abnormal blood routine and biochemical indices, or unstable liver functions. The presence of newborn tissues was identified within the 60 days post-implantation. No significant differences were observed between the three groups (P < 0.05). The wide clinical application of HA/PLGA/BMP-2 composite biomaterial, which is highly compatible with rabbits with no apparent effects on the animals, is highly feasible.