AbstractQueen honey bees (Apis mellifera) have a much longer lifespan than worker bees; however, the longevity-promoting mechanisms of queen bees are still unclear. Assaying cellular activities can explore the longevity-promoting mechanisms of queen bees because the longevity of individuals is based on the longevity of their cells. In this study, NAD+ levels, NAD+/NADH ratio, ATP levels, AMPK activity, lysosome activity, and ribosomal protein S6 mRNA levels were assayed to evaluate whether queen bees have higher cellular activities than worker bees. The results showed that the trophocytes and oenocytes of queen bees have higher cellular activities than that of worker bees. To explore which signaling pathway increases these cellular activities, the cAMP concentration and the mRNA levels of AC, PKA, RAS, MEK, and RSK were assayed. The results showed that the trophocytes and oenocytes of queen bees exhibit higher cAMP concentration and mRNA levels of AC, PKA, RAS, MEK, and RSK than that of worker bees. Combining these findings suggested that the cAMP/PKA and RAS/MAPK signaling pathways may increase cellular activities leading to the longevity of queen bees.