This research was designed to investigate changes of growth factors and bone matrix proteins during the bone healing processes using immunohistochemistry and in situ hybridization. Especially this study was focused on the changes of bone matrix and growth factors around the titanium implant. Threaded implants were introduced into the long bone of tibia. Time dependent changes of several bone associated protein and and its mRNAs were observed. Proteins investigated in this study are collagen, osteonectin(ON), osteopontin(OPN), osteocalcin(OC). Expression of the proteins were measured using immunohistochemistry. VEGF and ON were measured using in situ hybridization, and northen blot technique. Bone regeneration were observed as early as the third day of experiment. Matrix proteins and growth factors observed around implant were identical to the proteins observed in the control group. The expression of the ON, OC and VEGF were observed mainly in the osteoblast-like cell on the surface of new bone around the implant and the cells lining the margin of bone defect apart from the implant. The observation may not result from direct osteoconducting activities of titanium but by passive adsorption of extracellular factors which has bone inducing capacities. These passive adsorption results in the immobilization of the growth factors and consequent prolongation of the activities.