〔Abstract〕 Objective To explore the mechanism of dexmedetomidine in alleviating cognitive dysfunction in aged rats after anesthesia from the level of cerebrospinal fluid autophagy. Methods 40 rats were randomly divided into four groups (10 rats in each group), control group, propofol group (pro group, intraperitoneal injection of 80 mg·kg-1 propofol), PRO+10 μg·kg-1 dexmedetomidine group (intraperitoneal injection of 80 mg·kg-1 propofol+intraperitoneal injection of 10 μg·kg-1 dexmedetomidine), PRO+20 μg·kg-1 dexmedetomidine group (intraperitoneal injection of 80 mg·kg-1 propofol+intraperitoneal injection of 20 μg·kg-1 dexmedetomidine). The cognitive function was tested by Morris water maze (MWM), test and the cerebrospinal fluid (CSF) was extracted for Western blot and immunofluorescence analysis. Results In this study, the results showed that propofol exposure on the 6th day after anesthesia reduced the autophagy, while dexmedetomidine restored impaired autophagic energy. The expression of LC3B in cerebrospinal fluid was analyzed by immunofluorescence. It was found that the staining of LC3B in PRO group was significantly lower than that in other three groups, which was consistent with the quantitative analysis of Western blot. Compared with PRO group, LC3B staining increased significantly in 10 μg·kg-1 dexmedetomidine group and 20 μg·kg-1 dexmedetomidine group, which was consistent with Western blot. Conclusion Dextrometridine can improve the learning and memory impairment induced by anesthesia in aged rats, which is related to the up-regulation of the inhibition of cerebrospinal fluid autophagy in aged rats.