Sirtuin 1 (SIRT1) exerts a neuroprotective effect in various neurologic diseases. Here we investigated the protective functions of SIRT1 in astrocytes, which are the most abundant cells in the central nervous system. Upregulation of SIRT1 suppressed the expression levels of pro-inflammatory cytokines and increased the expression levels of superoxide dismutase 2 and catalase. Inversely, inhibition of SIRT1 significantly increased acetylation of forkhead box protein O4, decreased the expression levels of superoxide dismutase 2 and catalase, and increased the production of reactive oxygen species. Our data suggest that astrocytic SIRT1 may elicit neuroprotective effects through its anti-oxidative and anti-inflammatory functions.