A edible cuttlefish(Zoological name : Sepia esculenta) bone has a porous structure with all pores interconnected The purpose of this research is to develop porous hydroxyapatite prepared by hydrothermal treatment from cuttlefish bone and evaluate the biocompatibility using undecalcified materials through the in-vivo test of rabbits. In this study, the phase and substructure of a porous hydroxyapatite, prepared by hydrothermal treatment using edible cuttlefish bone as a calcium source, has been confirmed by X-ray diffractometer and scanning electronic microscope. After preparing the specimens with 5mm diameter and 7mm length, the specimens were implanted into the femoral condyles of rabbits. Each rabbits were sacrificed at each time period of 1, 2, 3, 4 weeks after operation, respectively and the stained section was examined by a transmission light microscope. The X-ray diffraction patterns of the edible cuttlefish bone was confirm for aragonite phase and of the sample after hydrothermal treatment showed mostly into hydroxyapatite phase. There was more bone density increase in porous HA rod around implant site than natural edible cuttlefish bone. Because the edible cuttlefish bone is a very pure and good calcium source, porous hydroxyapatite developed from this study is expected to be a biomaterial having a good biocompatibility to be used as a suitable bone substitute.