Abstract: Retina and pineal gland are developmentally related and also share expression of many genes involved in phototransduction. One of them is Retinoschisin (RS1), which is a 224 amino acid protein expressed exclusively by photoreceptors/bipolar cells and pinealocytes. RS1 maintains the retinal architecture and structure of the photoreceptor-bipolar synapse in retina, but the basic biology of RS1 protein in pineal gland remains poorly understood. Here we evaluated RS1 expression in the pineal body of rat and mouse at different age, and looked for morphological changes in the pineal gland of the rat and RS1 knock-in mouse. Behavior experiments shown that diminish circadian rhythm and the disturbance of chronobiology have observed in both aging rat and RS1-KI mice, and RS1-KI mice have the depressive-anxious disorders. We found that RS1 exhibited gradually increases of different intensity with increasing age and negatively related to the number of the pinealocytes. Furthermore, co-localization of retinoschisin with Cx36 and ZO-1 like aggregations is homologous to the association of retinoschisin with basement membranes elements in the pineal gland. We propose that RS1 may be required for a molecular basis of the architecture between pinealocytes in the rodent and associated with junctional complex serve to support the rhythmic activities of pineal gland. Together, these observations provide new insights into the physiological function role of RS1 in the pineal gland.