Objective To investigate the changes of synaptotagmin-Ⅰ(syt-Ⅰ) in in adult mice after sevoflurance anesthesia. Methods　One hundred and twenty 16-week male C57BL/6 mice, weighing (21.2±2.2) g, were randomly divided into 4 groups (n=30) using a random number table: group O2+normal saline+pelltobarbitalum natricum(group C), group O2+normal saline+laparotomy surgery+pelltobarbitalum natricum(group S), group sevoflurance anesthesia+laparotomy surgery+normal saline(group SS) and group sevoflurance anesthesia+laparotomy surgery+dexamethasone(group SD). Animals in group SD were subjected to an administration of dexamethasone(2 mg/kg), other groups were subjected to isochoric normal saline 1 h before anesthesia. Group C and group S were anesthetized with pelltobarbitalum natricum（1.5%， 0.1 ml/20 g）. Group SS and group SD were anesthetized with sevoflurane(3.4%~3.6%). Group C was subjected to no surgery, while other 3 groups were subjected to laparotomy surgery. The Morris water maze test were performed at 24 h after the anesthesia and surgery, and record the escape latency, frequency of crossing the original platform, and duration of swimming spent at the target quadrant, the fear conditioning training was performed 2 h later. The contextual and cued fear conditioning test were peformed at 24 h after training. The hippocampus was harvested after the behavioral test immediately to determine the expression of syt-Ⅰ, IL-1β and S100A8(by Western blot) and the expression of mRNA of S100A8, toll-like receptor 4(TLR4), IL-6, IL-1β, TNF-α(by RT-PCR).　Results　Compared with group C, the escape latency was increased in Day 3, Day 4 and Day 5(P<0.05), the crossing platform times were decreased, crossing platform quadrant time, the freezing time in the contextual fear conditioning test were shortened in both group S and group SS(P<0.05). Compared with group SS, the frequency of crossing the original platform, duration of swimming spent at the target quadrant, and freezing time in the contextual fear conditioning test were increased(P<0.05), the escape latency was shortened in group SD(P<0.05). There was no significant difference in the freezing time in the cued fear conditioning test among the four groups. Compared with group C, the content of IL-1β and S100A8 protein were increased(P<0.05), and IL-1β, S100A8, TNF-α mRNA were increased(P<0.05) in the group S and group SS. Compared with group C, the content of syt-Ⅰ and TLR4 mRNA was decreased(P<0.05), and S100A8 mRNA and IL-1β mRNA were expressed more in group SS(P<0.05).　Conclusions　Down regulation of syt-Ⅰin hippocampal neurons is involved in cognitive dysfunction caused by single sevoflurance anesthesia of high concentration and surgery.