The　aim　of　this　study　was　to　elucidate　the　signaling　pathway　involved　in　the　anti-aging　effect　of　erythropoietin　(EPO)　and　to　clarify　whether　recombinant　human　EPO　(rhEPO)　affects　apoptosis　in　the　aging　rat　hippocampus　by　upregulating　Sirtuin　1　(SIRT1).　In　this　study,　a　rat　model　of　aging　was　established　using　D-galactose.　Behavioral　changes　were　monitored　by　the　Morris　water　maze　test.　Using　immunohistochemistry,　we　studied　the　expression　of　SIRT1,　B-cell　lymphoma/leukemia-2　gene　(Bcl-2),　and　Bcl-2　associated　X　protein　(Bax)　expression,　and　apoptotic　cells　in　the　hippocampus　of　a　rat　model　of　aging　in　which　rhEPO　was　intraperitoneally　injected.　The　escape　latency　in　rats　from　the　EPO　group　shortened　significantly;　however,　the　number　of　platform　passes　increased　significantly　from　that　in　the　D-gal　group　(P　＜　0.05).　Compared　to　the　D-gal　group,　in　the　EPO　group,　the　number　of　SIRT1　and　Bcl-2-positive　cells　increased　(P　＜　0.05),　but　the　number　of　Bax-positive　cells　and　apoptotic　cells　decreased　in　the　hippocampus　of　aging　rats　(P　＜　0.05).　These　results　suggest　that　rhEPO　regulates　apoptosis-related　genes　and　affects　apoptosis　in　the　hippocampus　of　aging　rats　by　upregulating　SIRT.　This　may　be　one　of　the　important　pathways　underlying　the　anti-aging　property　of　EPO.