Objective The study is to investigate the neuroprotective effect of different doses of Maresin1 pretreatment in aged rats after anesthesia/surgery and the related mechanisms. Methods Aged male rats were randomly divided into a control group, an anesthesia/surgery group, and low, medium, and high-dose Maresin1 pretreatment groups, and the hippocampus was taken for study. The Morris water maze was performed to detect the cognitive ability of rats. Western blot and immunofluorescence were used to detect the expression of glial fibrillary acidic protein (GFAP) and central nervous system-specific protein (S100β). The ultrastructure of astrocytes was observed by a transmission electron microscope. Quantitative real-time PCR was used to detect the relative expression of IL-1β, IL-6, and TNF-α mRNA. Results Compared with the control group, the cognition of rats in the anesthesia/surgery group was significantly reduced. The expression of astrocyte markers (GFAP and S100β) in the hippocampus of rats in the anesthesia/surgery group was increased. The levels of hippocampal inflammatory cytokines (TNF-α, IL-1β, and IL-6) were also higher in the anesthesia/surgery group than in the control group. After pretreatment with different doses of Maresin1, the cognitive impairment of rats was alleviated to varying degrees. Maresin1 pretreatment decreased the expression of astrocyte markers and inflammatory factors in the hippocampus of rats after anesthesia/surgery, and improve the microstructures of activated astrocytes, especially in the medium-dose group. Conclusion Pretreatment with Maresin1 (especially at medium-dose) showed neuroprotective effects in aged rats after anesthesia/surgery, which may be related to the inhibition of astrocyte activation.