Iodine is an essential component of the thyroid gland hormones (T3 and T4), necessary for mammalian life. Iodine deficiency leads to inadequate thyroid hormone production, and all the consequences of iodine deficiency stem from the associated hypothyroidism. Iodized oil is made by treating a fatty vegetable oil with iodine or hydriodic acid and is an effective long-term means of iodine supplementation. The type and fatty acids profile in the parent oil, as well as the way iodine is trapped, affect the physicochemical properties and effectiveness of the product. This research was conducted to study the effect of iodinated safflower oil on preventing iodine deficiency disorders (IDD) in livestock, compared with a commercial iodine supplement. Iodinated fatty acid ethyl esters prepared from safflower seed oil (IFAEESSO). Thirty Farahani ewes with a history of iodine deficiency were divided into three groups, including control and two treatment groups. The treatment groups received 390 mg of iodine by an intramuscular injection of 1.26 ml of IFAEESSO (n = 10) or 1.5 ml of Depodine® (n = 10), respectively. Serum iodine, thyrotropin stimulating hormone (TSH), T3 and T4 concentrations were assayed at baseline and every 30-day intervals over six months period. Iodine supplementation resulted in a significant increase in serum inorganic iodine over five months with Depodine and IFAEESSO (P < 0.01). Serum T3 and T4 concentrations also increased in treatment groups (P < 0.01), while the concentration of TSH didn’t change. The mean T4 and T3 concentrations were 3.16 μg /dl and 53.89 ng /dl in the control group, which increased to 3.50 μg /dl and 58.88 ng/dl for Depodine and 3.88 μg /dl and 63.55 ng/dl for IFAEESSO, respectively. The serum inorganic iodine and thyroid hormone concentrations were significantly higher in the IFAEESSO group than in the Depodine group (P < 0.01). IFAEESSO is an effective supplement against IDD and more efficient than that of Depodine to increase serum iodine concentration, and thyroid hormone production.