Objective To investigate the effect of different concentrations of Sevoflurane on oxidative stress and caspase-9 expression in rats. Methods Eighty clean grade healthy male SD rats at the age of 18 months were selected and randomly divided into 5 groups according to the random number table method, each group had 16 rats. The rats in the group A inhaled 0% Sevoflurane and 2 L/min O2 for 6 h, the rats in the group B1 inhaled 1% Sevoflurane and 2 L/min O2 for 6 h, the rats in the group B2 inhaled 2% Sevoflurane and 2 L/min O2 for 6 h, the rats in the group B3 inhaled 3% Sevoflurane and 2 L/min O2 for 6 h, the rats in the group B4 inhaled 4% Sevoflurane and 2 L/min O2 for 6 h. At 24 h after Sevoflurane anesthesia, water maze test was carried out, the levels of amyloid precursor protein (APP), β-amyloid protein (Aβ1-42), malondialdehyde (MDA) and SOD in the hippocampi as well as the levels of inflammatory cytokines and caspase-9 expression were detected in the 5 groups of rats. And the results were compared and analyzed. Results The latent periods of the groups B3 and B4 were significantly different from that of the group A (P < 0.05). The swimming distance of the group B4 was significantly different from that of the group A (P < 0.05). The comparison of the number of times crossing through the platform and the residence time in the platform in the groups B2, B3 and B4 were significantly different from those in the groups A and B1 (P < 0.05), but there were no significant differences among the groups B2, B3 and B4 (P > 0.05). The expressions of Aβ1-42 and APP in the rat hippocampi of the group B1 had significant differences from those in the group A, the two indexes in the hippocampi of the groups B2, B3 and B4 were significantly different from those in the groups A and B1 (P < 0.05), there were no significant differences among the groups B2, B3 and B4 (P > 0.05). The β-site APP-cleaving enzyme-1 (BACE-1) expression in the hippocampi of the groups B1, B2, B3 and B4 increased gradually with the increase of the concentration of Sevoflurane, the expression levels of BACE-1 in the groups B4 and B3 were significantly higher than those in the groups A, B1 and B2 (P < 0.05), and thhere were also significantly difference between the two groups (P < 0.05). Compared with the group A, MDA content in the rat hippocampi increased with the increase of Sevoflurane concentration, while SOD content decreased in the groups B1, B2, B3 and B4; MDA content of the groups B3 and B4 was significantly higher than that of the group A, while SOD content was significantly lower than that of the group A (P < 0.05). Compared with the group A, the expressions of IL-6 and IL-8 in the hippocampi of the rats increased with increase of Sevoflurane concentration in the groups B1, B2, B3 and B4; and the expressions of IL-6 and IL-8 in the groups B2, B3 and B4 were significantly different from those in the group A (P < 0.05), but there were no significant differences between the group B1 and the group A (P > 0.05). Compared with the group A, the caspase-9 expression in the rat hippocampi increased significantly with increase of Sevoflurane concentration in the groups B1, B2, B3 and B4; the caspase-9 expression in the groups B3 and B4 was significant different from that in the group A (P < 0.05), while the comparison between the groups B1 and B2 with the group A showed no significant differences (P > 0.05). Conclusions The occurrence of postoperative cognitive dysfunction in aged rats is closely related to Sevoflurane, the characteristic is concentration-dependence. When the Sevoflurane concentration is higher than 3%, the cognitive function in aged rats changes significantly after anesthesia. Its mechanism may be related to production of APP and Aβ, induction of oxidative stress, the promotion of inflammation and cell apoptosis.