Objective:To evaluate the effect of oxiracetam on sevoflurane-induced cognitive dysfunction in mice and the role of phosphatidylinositol 3-kinase/serine/threonine protein kinase (PI3K/Akt) signaling pathway.Methods:Eighty adult Kunming mice, half male and half female, weighing 35-55 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), sevoflurane group (group S), oxiracetam plus sevoflurane group (group OS), and LY294002 plus oxiracetam plus sevoflurane group (group LOS). Group S inhaled 2% sevoflurane for 6 h. A 2 h before sevoflurane anesthesia, oxiracetam 105 mg/kg was injected via the tail vein in group OS, oxiracetam 105 mg/kg and LY294002 0.3 mg/kg were injected via the tail vein in group LOS, and the equal volume of normal saline was injected in group S. The apoptosis rate of hippocampal neurons was detected using TUNEL.The expression of PI3K, phosphorylated PI3K (p-PI3K), Akt and phosphorylated Akt (p-Akt) was determined by Western blot.Cognitive function was assessed using Y-maze at 14 days after the end of anesthesia. Results:Compared with group C, the apoptosis rate of hippocampal neurons was significantly increased, the total number of times and the number of errors required for 10 times of correct responses in Y-maze test were increased, and the expression of PI3K, Akt p-PI3K and p-Akt in hippocampal tissues was down-regulated in group S ( P<0.05). Compared with group S, the apoptosis rate of hippocampal neurons was significantly decreased, the total number of times and the number of errors required for 10 times of correct responses in Y-maze test were decreased, the expression of PI3K, Akt, p-PI3K and p-Akt in hippocampal tissues was up-regulated in group OS ( P<0.05), and no significant changes were found in the parameters mentioned above in group LOS ( P>0.05). Compared with group OS, the apoptosis rate of hippocampal neurons was significantly increased, the total number of times and the number of errors required for 10 times of correct responses in Y-maze test were increased, and the expression of PI3K, Akt, p-PI3K and p-Akt in hippocampal tissues was down-regulated in group LOS ( P<0.05). Conclusion:Oxiracetam can alleviate sevoflurane-induced cognitive dysfunction in mice, and the mechanism may be related to activating PI3K/Akt signaling pathway and inhibiting apoptosis in neurons.