Objective <p>Postoperative neurocognitive disorders (NCD) are common complications following general anesthesia, yet their underlying mechanisms remain poorly understood. This study investigates the impact of isoflurane anesthesia on astrocyte connexin 30 (Cx30) expression in the hippocampus.</p> Methods <p>Eighteen 8-month-old male Sprague–Dawley rats were divided into three groups: control, post-anesthesia 1-day, and post-anesthesia 3-day groups. Rats in the anesthesia groups were exposed to 1.8% isoflurane for 2 h. Hippocampal tissues were collected at 1 and 3 days post-anesthesia. Cx30 expression was assessed using Western blot (WB) and immunofluorescence staining. Protein levels were quantified, and statistical analysis was performed using one-way ANOVA with Bonferroni post hoc tests.</p> Results <p>WB analysis revealed a significant reduction in Cx30 protein expression in the hippocampus of rats at both 1 and 3 days post-isoflurane anesthesia compared to controls. Immunofluorescence staining confirmed decreased Cx30 expression in hippocampal astrocytes, consistent with WB findings.</p> Conclusion <p>Isoflurane anesthesia significantly reduces Cx30 expression in hippocampal astrocytes, which might be related with the mechanism of postoperative NCD. These findings highlight the role of astrocyte Cx30 in synaptic function and cognitive processes, implicating its dysregulation in the pathophysiology of anesthesia-induced cognitive impairment. Further research is needed to explore the functional consequences of Cx30 alterations and their contribution to postoperative NCD.</p>