Objective · To detect the effects of propofol on rat hippocampal astrocytes and clarify its mechanism. Methods · According to the time after propofol injection, twenty-four SD rats were randomly divided into three groups, i.e. 0 min, 45 min and 90 min group. Rats were administrated intraperitoneally with propofol (10 mg/mL, 100 mg/ kg body weight). The levels of glial fibrillary acidic protein (GFAP) and S100β mRNA in rat hippocampus were evaluatedrealtime PCR. And cell viabilities and levels of GFAP mRNA were examined in primary cultured hippocampal astrocytes induced10 μmol/L propofol with or without 10 μmol/L extracellular signal-regulated kinase (ERK) inhibitor PD98059 pretreatment. Results · The mRNA levels of GFAP in the hippocampal tissue were (1.32±0.12) times (P0.000) and (1.12±0.09) times (P0.012) that in 0 min group, respectively,45 min and 90 min after injection of propofol. The mRNA levels of S100βin the hippocampal tissue were (1.14±0.11) times (P0.005) and (1.05±0.10)times (P0.284) that in 0 min group, respectively, 45 min and 90 min after injection of propofol. The mRNA levels of GFAP and S100β were time-dependently altered, first increasing, and then decreasing. In vitro, the cell viabilities (P0.041) and levels of GFAP mRNA (P0.026) in primary cultured hippocampal astrocytes were significantly elevated after propofol treatment, and these effects of propofol were reversedERK inhibitor PD98059.Conclusion · Propofol time-dependently upregulated the of GFAP and S100βvia ERK signaling pathway in rat hippocampal astrocytes, so as to activate astrocytes.