Background and objectives: Thyroid hormone exercises vital role in the event of development of central nervous system in stage of fetal life, childhood, and maintains tropic action in adulthood and also in aging. Deficiency in thyroid hormones responsible for impairment of mental performance. Inadequate iodine intake was is the major health problem. Use of iodized salt is now in vogue globally including India to eradicate iodine deficiency disorders (IDDs). This salt iodization should be at par to the iodine content of environment or water. Hilly areas have low iodine content whereas in coastal areas have higher iodine content in vegetables and water; however the people of both the areas are consuming uniform iodine containing salt. Therefore there is a chance of consuming excess iodine of the people in environmentally iodine sufficient areas. So far the effect of excess iodine specially in brain in relation to thyroid gland function yet have not been extensively investigated. Materials and method: For the study 36 number of rats weighing 120±10g of 90±5 days old, primarily divided into two groups on the basis of the duration of treatment viz. 30 days group and 60 days group respectively and on the exposure of the dose of iodine was divided in to two sub-group, excess iodine exposed group (100HI), was gavaged orally potassium iodide (KI) at the dose of 7 mg/Kg body weight and excessive iodine group (500HI) was gavaged orally KI at the dose of 35mg/Kg body weight. Results: Our overall result revel that those doses of excessive iodine causes a state of hypothyroidism as manifested by serum T3 serum T4 and TSH levels and thyroid morphology and also alters of cholinergic homeostasis in different areas of brain as revealed by acetylcholinesterase and Na+-K+ ATPase activity. Conclusion: Excessive iodine with higher dose and duration causes hypothyroidism which is responsible for alteration of cholinergic homeostasis in different region of brain. © 2016, International Journal of Pharmaceutical and Clinical Research. All rights reserved.