The study aims to explore the effects of microRNA‐206 (miR‐206) targeting IGF‐1 on the activation of hippocampal astrocytes in aged rats induced by sevoflurane through the PI3K/AKT/CREB signaling pathway. Wistar rats and astrocytes were divided into the normal/blank, sham/negative control (NC), sevoflurane (sevo), miR‐206 mimics + sevo, miR‐206 inhibitors + sevo, miR‐206 NC + sevo, IGF‐1 shRNA + sevo and miR‐206 inhibitors + IGF‐1 shRNA + sevo groups. The Morris water maze test was exhibited to assess the cognitive functions. Glial fibrillary acidic protein (GFAP) expression was detected by immunofluorescence assay. Western blotting and RT‐qPCR were used to detect the expression of miR‐206, IGF‐1, PI3K, AKT, CREB, pPI3K, pAKT, pCREB, cytochrome‐c (Cyt‐c) and caspase‐3. Cell viability and apoptosis were detected by MTT assay and Annexin V/PI double staining respectively. Mitochondrial transmembrane potential (MTP) were determined by flow cytometry. The IGF‐1 shRNA + sevo group showed reduced miR‐206 expression. Compared with the normal/blank group, the sevo and miR‐206 NC + sevo groups showed decreased miR‐206 and GFAP expressions, cell viability and MTP but increased expressions of IGF‐1, PI3K, AKT, CREB, pPI3K, pAKT, pCREB, Cyt‐c and caspase‐3, as well as cell apoptosis. Similar trends were observed in the miR‐206 inhibitors + sevo group when compared with the sevo group. The study provides evidence that miR‐206 alleviates the inhibition of activation of hippocampal astrocytes in aged rats induced by sevoflurane by targeting IGT‐1 through suppressing the PI3K/AKT/CREB signaling pathway. This article is protected by copyright. All rights reserved