Objective To evaluate the effect of isoflurane on the expression of hippocampal ubiq-uitin C-terminal hydrolase-L1(UCH-L1)mRNA in aged rats. Methods Thirty-six pathogen-free healthy male Sprague-Dawley rats, aged 20 months, weighing 500-700 g, were divided into 2 groups using a ran-dom number table: control group(group C, n=12)and isoflurane group(group I, n=24). In group I, 2% isoflurane was continuously inhaled for 2 h. Twelve rats were selected at 24 and 72 h after stopping isoflurane inhalation(T1,2), and Y-maze test was performed to evaluate cognitive function. The animals were sacrificed after the end of Y-maze test and their hippocampi were removed for determination of UCH-L1 expression(by immuno-histochemistry)and UCH-L1 mRNA expression(by real-time polymerase chain reaction). Results Compared with group C, the total number of training achieving the standard was sig-nificantly increased at T1(P<001 or 005), and the expression of UCH-L1 mRNA was down-regulated, and no significant change was found at T2in group I(P>005). Conclusion The mechanism by which isoflurane induces cognitive decline may be related to down-regulating the expression of UCH-L1 mRNA in hippocampal tissues of aged rats.