Statement of problem. Mechanisms of tissue-implant interaction and the effect of the implant surface on the behavior of cells has not yet been clarified. Purpose. This study was performed to investigate the tissue reaction to the titanium alloy submerged into rat peritoneum in vivo. Materials and methods. Titanium alloys (titanium-13Zirconium-6Niobium) were inserted inside the peritoneal cavity of Sprague Dawley rats. After 3 months, the tissue formed around the inserted titanium alloys were examined with a light-microscope. Tissue reaction around the material was analyzed by confocal microscopy to evaluate their biocompatibility in a living body. Results. In in vivo study, foreign body type multinucleated giant cells were found in the fibrous tissue formed as a reaction to the foreign material (4 in 20 cases), but the inflammatory reaction was very weak. After experiment, the contaminants of biomaterials was removed from living tissue. In confocal microscopy, we observed that the staining of vinculin and actin showed mixed appearance. In a few cases, we found that the staining of vinculin and beta-catenin showed the prominent appearance. Conclusion. We found that titanium-13Zirconium-6Niobium alloy was an excellent biomaterial.