Immunity, a primeval feature of living organisms & is essential for reproduction and to face the challenges originating from seasonal variation and environmental threats as well. Present study reveals that how tropical animals have evolved a mechanism via melatonin to blaster the immune function to counteract seasonally recurrent stressors that may otherwise compromise immune functions. Finding suggests that melatonin is having an adaptive significance in balancing immune status in this rodent. It acts during winter as immuno-stimulator to save the squirrels from the adverse condition (environmental and internal high glucocorticoid level) and free radical load. The effect of melatonin is a direct one, since the receptor for melatonin (Mel 1a) was noted on lymphatic organs. Melatonin may act through/altering the other endocrine glands activity (thyroid/adrenal) in modulating the immune function according to the season. Such interdependency of melatonin-thyroxin and immune function may throw some light to the clinical problems of thyroid dysfunction and immune deficiency.