Elderly patients may experience a decline in cognition after a surgery performed under anesthesia. Propofol (2,6-diisopropylphenol), a common intravenous anesthetic agent, has been reported to mediate the long-term potentiation (LTP), a major form of synaptic plasticity. The present study was conducted to investigate the underlying mechanisms in young (3-month-old) and elderly (20-month-old) male rats. A decline of theta-burst stimulation (TBS)-induced LTP in the hippocampal CA1 area was found in the young rats at 72 h post-anesthesia, and this alteration almost disappeared after 2-week-recovery as compared with their age-matched control rats. On the other hand, the propofol-induced CA1 LTP reduction was persistent in the aged rats during the whole experimental process. Moreover, TBS-induced increases in CA 1 filamentous-actin (F-actin) polymerization and phospho-cofilin expression were enhanced at 72 h post-anesthesia in young rats, and this change was significantly attenuated after 2 weeks. However, in anesthetic elderly rats, the alterations in F-actin and phospho-cofilin of the CA1 region were still presented at the end of the experiments. Taken together, our results indicate that the discrepant responses between young and aged rats to propofol anesthesia may be associated with the differential polymerization of F-actin.