Background: Although it is well-known that thyroid stimulating antibody levels usually increase after radioactive iodine therapy, we observed various changes in thyroid stimulating antibody levels. Methods: We divided 47 patients who underwent radioactive iodine therapy into two groups based on thyroid stimulating antibody levels three months post-therapy, as follows: the D(3M) group with increasing levels and the I(3M) group with decreasing levels of the antibody. We compared the clinical characteristics of the two groups. In addition, the 47 patients were again divided into the following two groups, and their clinical characteristics were compared: the D(6M) and I(6M) groups, which consisted of patients with decreasing and increasing thyroid stimulating antibody levels, respectively, three to six months after radioactive iodine therapy. Results: A significantly higher dose of Iodine-131(I-131) per gram of estimated thyroid weight was observed in the D(3M) group than in the I(3M) group, suggesting that the removal of intrathyroidal immune cells by β-rays may influence changes in thyroid stimulating antibody levels. The D(6M) group had significantly higher goiter shrinkage rates than did the I(6M) group, at three, six, and 12 months post-radioactive iodine therapy. Since the goiter shrinkage rate is equivalent to the decreasing rate of thyroid antigen levels, we speculate that the reduction in thyroid antigen led to a decrease in thyrotropin receptor antibody production mediated by peripheral blood immune cells. Conclusions: Our study suggests that, in the short-term, thyroid stimulating antibody levels after radioactive iodine therapy were significantly associated with the receipt of radioactive iodine therapy, probably due to the reduction in the number of intrathyroidal immune cells, and, in the long-term, they were influenced by the immune response of peripheral blood cells associated with the reduction in thyroid antigen by I-131. Therefore, high-dosage I-131 therapy is recommended for Graves’ patients who do not desire total thyroidectomy and are planning to become pregnant, or those with a risk of ophthalmopathy.