It is difficult to treat the endodontic apical perforation successfully. In this study, we hypothesized that the application of PDGF-BB and IGF-I into periapical perforation site may accelerate periapical healing and lead to bone deposition. And the specificity of osteonectin in periapical healing was investigated. The experiments were performed on the upper and lower 51 premolar teeth of 4 beagle dogs. The pulp chamber of each tooth was opened and the dental plaque was inserted into the canal for developing the periapical lesion for 5 weeks. Then, the roots were artificially perforated at the apex with the number 4 profile of .06 taper. In each step, standard periapical radiographs were taken to compare the size of lesion each other. The radiographs were scanned and analyzed by image analysis system. The mean and standard deviation of periradicular radiolucency ratios were calculated in each group. ANOVA was used for comparison. 51 premolars were grouped into 3 groups; control group, calcium hydroxide-treated group and calcium hydroxide plus growth factors-treated group. In the control group, the apical perforations were not sealed and obturated with gutta-percha and ZOE sealer by lateral condensation technique. In the experimental groups, the apical perforation were sealed with calcium hydroxide and with/without $4{mu}g$ of PDGF-BB & IGF-I in cellulose gel and obturated by lateral condensation technique. Fluorescent bone markers were used to measure new bone formation. Following 2, 4, 12 weeks after experiment the dogs were sacrificed and histologic sections were prepared. Each tooth block including periapical lesion was sectioned mesiodistally. One half of the sections were decalcified with 6% nitric acid and processed by standard paraffin embedding technique. The sections were stained by hematoxylin and eosin, and immunostained for osteonectin. Histomorphometrical measurement of neoformed bone was performed using a light microscope. And the other half of the sections were prepared by undecalcified preparation, and confocal laser scanning microscopic investigations were done.