Objectives: The development of thyroid tumor has a relationship with carcinogen, oncogene and tumor suppressor gene. With aminotriazole, radioactive iodine and nitrosomethylurea as carcinogens in rat, authors investigate the incidence in type of the thyroid tumors, p21 and p53 protein expression pattern by immunohistochemical stain and the relationship between the tumors and p21-p53 protein expressions. Materials and Methods: 80 experimental animals were divided into four groups; group 1(control, no carcinogen, n=20), group 2(oral administration of aminotriazole for 36 weeks, n=20), group 3(intraperitoneal injection of 131I for one time and oral administration of aminotriazole for 36 weeks, n=20), group 4(oral administration of nitrosomethylurea for 3 days and aminotriazole for 36 weeks, n=20). After 40 weeks they were sacrificed with pathologic examination and we performed immunohistochemical staining with pan-ras monoclonal antibody for p21 protein and CMI polyclonal antibody for p53 protein with paraffin-embedded specimens. Results: 1) No tumors were observed in group I, but 38.3% of nodular goiters, 11.7% of adenomas and 50.0% of carcinomas were observed in carcinogen treated groups(group 2, 3, 4). 2) The incidence of nodular goiter, adenoma and carcinoma were 70%, 20% and 10% in group 2, 40%, 15% and 45% in group 3 and 5%, 0% and 95% in group 4. 3) p21 protein was not expressed in normal thyroid tissues but was expressed in 26.1% of nodular goiters, 42.9% of adenomas and 6.7% of carcinomas. On the other hands, p53 protein was not expressed in normal thyroid tissues, nodular goiters, adenomas and in well differentiated thyroid carcinomas by immunohistochemical stain. Conclusion: The authors suggest that aminotrizole, 131I, nitrosomethylurea can be etiologic agents in the development of thyroid tumor and the p21 protein can be expressed in the early stage and in benign condition of thyroid tumor but p53 protein is not expressed in all conditions of development in rats.