Objective To investigate the effect of sevoflurane anesthesia on the expression of hippocampal apolipoprotein E (ApoE) mRNA of rats. Methods Sixty healthy male Sprague-Dawley rats, weighing 300-400 g, aged 15 weeks, were randomly divided into 2 groups (n=30 each) using a random number table: 50% oxygen group (group C) and 3.2% sevoflurane group (group S). The rats in group C inhaled 50% oxygen for 2 h, while those in group S inhaled 3.2% sevoflurane in 50% oxygen for 2 h. Morris water maze test was carried out before anesthesia and at 24 and 72 h after anesthesia. At 2, 24 and 72 h after anesthesia, hippocampal specimens were obtained for determination of the expression of ApoE mRNA by RT-PCR. Results Compared with group C, no significant change was found in the escape latency, time of staying at the original platform quadrant, frequency of crossing the original platform, and swimming distance before and after anesthesia, and the expression of ApoE mRNA was up-regulated after anesthesia in group S. There was no significant difference in the escape latency, time of staying at the original platform quadrant, frequency of crossing the original platform, and swimming distance before and after anesthesia, and expression of ApoE mRNA at each time point after anesthesia between the two groups. Conclusion Cognitive dysfunction induced by sevoflurane has no relationship with the up-regulated expression of ApoE mRNA in the hippocampus of rats. Key words: Anesthetics, inhalation; Cognition disorders; Apolipoproteins E