The purpose of this study was the observe the toxic effects of root canal sealers in 108 white rats. Experimental animals were divided into control and experimental groups. Theree representative types of materials, such as AH26, Z.O.E. and F.R. were used in this study. Cavities were prepared on the left mandibular area of 108 white rats. Three different sealers were placed in as experiment and bone cavities were left without filling as control. The experimental animals were sacrificed by cervical dislocation at the intervals of 1, 3, 7, 14, 28 and 49 days after filling. Each specimen was fixed with 10% neutral formalin solution, decalcified with 5% nitric acid, embedded in paraffin and sectioned 5-7${mu}$. in thickness. The paraffin sections stained with Hematoxylin - Eosin were observed through the ordinary light microscope. The results were as follows; 1. Slight toxic effect to surrounding tissue were found in every experimental specimen. 2. AH26 showed the highest inflammatory response, and F.R. showed the lowest inflammatory response which subsided and replaced by fibrosis at 4 weeks after filling. 3. The cavity filled materials, such as implanted root canal sealers, blood clots and necrotic tissue, showed a tendency to be absorbed gradually proportioned to the experimental periods. A small amount of cavity filled materials were observed in the bone cavities after 4 weeks. 4. Fibroblastic proliferation began to produce fibrous capsule around the bone cavity in 2 weeks after filling. Fibrosis was prominent at 4 weeks after filling. 5. Osteoblastic activity of surrounding bone was observed at first in 2 weeks after filling and prominent in 4 weeks after filling. Osteoblastic activity showed an increasing effect as the time prolonged. 6. Surrounding tissue of the bone cavities showed the features of tissue destruction and had very severe inflammatory response at an initial stage. Above-mentioned appeared to be recovered gradually proportioned to the experimental periods.