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The present study is designed to delineate the receptor mediated effect of melatonin in pituitary gland regulated thyroid secretions of hyperthyroid mice. Immuno histochemical study has been done to observe the melatonin receptors localization in pituitary gland. Western blot analysis was carried out to assess the expression patterns of melatonin receptors in pituitary gland and TSH receptors in thyroid gland. Hormonal analysis was done by ELISA kits. It was observed that introduction of melatonin reduced serum T3, T4, TSH hormones levels including thyroid TSH receptors those were fluctuated due to experimentally induced hyperthyroidism. The result has also shown the depletion of MT1 and MT2 receptors of pituitary gland due to melatonin treatment in hyperthyroidism. It may conclude that melatonin effects in pituitary regulated thyroid secretions by down regulation of pituitary MT1 and MT2 receptors in hyperthyroid condition.