Objective: To observe the immune response after the transplantation of a deproteinized heterogeneous bone scaffold and provides the theoretic reference for clinical practice. Methods: The fresh pig bone and deproteinized bone were transplanted respectively to establish BABL/C thigh muscle pouches model of male mice and take the samples for detection at 1, 2, 4, 6 weeks after operation. Lymphocyte stimulation index, subset analysis, serum specific antibody IgG, cytokine detection and topographic histologic reaction after implantation were investigated. Results: After the transplantation of deproteinized bone, lymphocyte stimulation index, CD4+ and CD8+ T-lymphocyte subsets, serum specific antibody IgG and cytokines in deproteinized bone group were significantly lower than those in fresh pig bone group at each time point (P<0.05). The histological examination found that in fresh bone group at each time point, a large quantity of inflammatory cells infiltrated in the surrounding of bone graft, and they were mainly lymphocytes, including macrophages and monocytes. In deproteinized bone group, there were few inflammatory cells infiltration around bone graft one weekafter operation.The lymphocytes were decreased as time went by.At 6 weeks,fibroblasts and fibrous tissue grew into the graft,and osteoclasts and osteoprogenitor cells appeared on the verge.Conelusions:The established heterogeneous deproteinized bone has low immunogenicity and is a poten-fially ideal scaffold material for bone tissue engineering.