Iodine is a natural mineral essential for good health and highly concentrated in thyroid tissue. It is used for diagnostic purposes as well as for therapeutic means. The present study was conducted to evaluate the effect of a single dose of iodine administration and multiple doses of the drug for a short and long term therapy on the periodontium. Sixty male albino rats were participated in the study. Twenty rats were used as a control group, the rest of the animals were divided into two experimental groups. The first group received single dose (diagnostic dose) of iodine. The second experimental group was divided into two subgroups. The first subgroup received multiple doses of iodine for a short period of 15 days, while the second subgroup received the same multiple doses for one month. Three rats of the control group and four of each experimental group were sacrificed at the end of the first, second, third and fourth weeks from the beginning of the study. Maxillary and mandibular specimens were dissected, stained with H. & E. and examined microscopically. The results of the study revealed that single diagnostic dose of iodine has no effect on the periodontium while multiple doses of the drug used for therapeutic purposes caused degeneration of periodontal tissues. The effect increased when the drug is used for a long period, the effect of the drug may be related to the direct effect of iodine concentrated in saliva on living cells or indirectly through the effect of xerostomia induced by the drug.