Aging has potent effects on many basic parameters of circadian rhythm and also are associated with impairments in learning and memory. Melatonin, a hormone mainly secreted in the pineal gland, is believed to restore circadian rhythm of clock genes in the suprachiasmatic nucleus during aging. The present study attempted to examine the daily profiles of different clock genes, and the clock-controlled cognition-related gene during development and aging and examine the effect of melatonin on the expression of these genes during aging in rat hippocampus. The results showed that the mRNA of the clock genes did not exhibit rhythmicity in the early postnatal period. Rhythmic expression of Period (Per)1 and Per2 began at P32 and was lost by 12 months of age, whereas the brain and muscle ARNT-like protein-1 (Bmal1) began at 2 months of age and was lost by 24 months of age. The clock-controlled cognition-related gene brain-derived neurotrophic factor (BDNF) mRNA also displayed a circadian rhythm at adulthood and lost its rhythmicity by 12 months of age. In the 24-month-old groups, all genes showed loss of rhythmicity and lower expression. Melatonin administered in drinking water for 2 months was able to rescue the loss of rhythmic expression of Per1, Per2, Bmal1, BDNF as well as melatonin receptors. The present study suggested that melatonin restored age-induced desynchronization in the expression of circadian genes in the hippocampus probably through its receptors. However, the mechanism by which melatonin alters this age-induced change remains unclear and requires further elucidation.