Objective To evaluate the role of calpain in sevoflurane anesthesia-induced apoptosis in hippocampal neurons of aged rats. Methods Fifty-four healthy female Sprague-Dawley rats, aged 18 months, weighing 450-550 g, were randomly divided into 3 groups(n=12 each)using a random number table: control group(group C), sevoflurane group(Sev group)and calpain inhibitor MDL28170 group(group M). In group C, the rats inhaled 50% O2-50%N2 for 3 h. In Sev group, the rats inhaled 3% sevoflurane for 3 h. In group M, MDL28170 10 mg/kg was injected via the tail vein, 30 min later 3% sevoflurane was inhaled for 3 h, and MDL28170 was simultaneously infused at 3.33 mg·kg-1·h-1 via the tail vein.Nine rats in each group were selected, and cognitive function was assessed by using Morris water maze test at 30 min before anesthesia and 1-5 days after anesthesia.The escape latency and frequency of crossing the original platform were recorded.After the end of Morris water maze test performed at 30 min before anesthesia and 1-5 days after anesthesia, 3 rats in each group were sacrificed, and hippocampal tissues were obtained for detection of cell apoptosis(by flow cytometry)and intracellular [Ca2+ ]i.Apoptotic rate was calculated. Results Compared with group C, the escape latency was significantly prolonged, and the frequency of crossing the original platform was decreased, and the apoptotic rate and intracellular [Ca2+ ]i were increased at 1 day after anesthesia in Sev and M groups.Compared with group Sev, the escape latency was significantly shortened, the frequency of crossing the original platform was increased, and the apoptotic rate was decreased at 1 day after anesthesia, and no significant change was found in intracellular [Ca2+ ]i in group M. Conclusion Calpain activation is involved in sevoflurane anesthesia-induced apoptosis in hippocampal neurons of aged rats. Key words: Calpain; Anesthetics, inhalation; Anesthesia; Aged; Apoptosis