Objective:To evaluate the effect of minocycline on the long-term learning and memory ability for 30 days afte surgery in C57BL/6 aged mice,and to explore the role of astrocytes in the process. Methords:Forty-five male C57/BL6 aged mice were randomly divided into 3 groups with 15 in each group:sham operation group only received skin incision,operation group received 70% hepatectomy without drugs administration,minocycline group intraperitoneally injected with 45 mg/kg minocycline once a day for 30 days after surgery. Hippocampal-dependent spatial learning and memory ability was evaluated using the Morris water maze(MWM). Then mice hippocampal tissue was sampled. The hippocampal mRNA relative expression levels of tumor necrosis factor α(TNF-α) and interleukin 6(IL-6) were tested using a real- time PCR. The expression levels of hippocampal glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1(Iba-1) were detected with Western blot. The remained hippocampal tissue was collected for immuno-histochemistry. Results:MWM tests showed that the escape latency and swimming distance in operation group was longer than that of sham and minocycline groups (P < 0.05). The relative expression of TNF-α mRNA of operation group was significantly higher sham and minocycline groups (P < 0.05),and the expression of TNF-α mRNA of minocycline group was less than operation group(P < 0.05). The expression of IL-6 mRNA in operation and minocycline group was significantly higher than that in sham group (P < 0.001),and the expression of IL-6 mRNA in minocycline groups was markedly less than that of operation group (P < 0.001). Compared with sham group,the expression of GFAP in operation and minocycline group was higher(P < 0.001),and the expression level of GFAP in minocycline group was less than that in operation groups(P < 0.001). There was no significant difference in Iba-1 expression among the three groups(P > 0.05). The changes of astrocytes in hippocampal tissue immunohistochemistry were consistent with the changes of GFAP. Conclusion:The activation of astrocytes in the hippocampus was likely to contribute to long-term decline of learning and memory ability in aged mice undergone partial hepatectomy. Minocycline can improve postoperative spatial learning and memory ability by decreasing the expression levels of TNF-a and IL-6 mRNA and inhibiting astrocyte activation.