Inhalation anesthesia with isoflurane is occasionally associated with the postoperative cognitive impairment and shift in the circadian rhythms. The microglial activation is suggested to be pathogenesis of these complications. Glucagon-like peptide 1 (GLP-1) is specifically expressed in microglia and are associated with circadian transcription factor in hippocampus. We previously reported that hippocampal GLP-1 is reduced with cognitive dysfunction. Therefore, we investigated whether the hippocampal GLP-1 is affected by surgery with inhalation anesthesia. The spatial working memory subjected by spontaneous alteration in the Y-maze is significantly decreased 24 hours in mice with 2h-exposure of isoflurane plus abdominal surgery. In addition, circadian rhythms are significantly shifted during 7 days social isolation after the 2h-exposure of isoflurane with surgery. Western blotting revealed that the protein level of GLP-1 was decreased to the subdetection level for more than three days after the inhalation anesthesia with isoflurane plus abdominal surgery. These results indicate the possibility that the GLP-1 may contribute to the postoperative cognitive dysfunction and shift the circadian rhythms.