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Background: Sevoflurane preconditioning improves brain function in MCAO rats, and there are several methods for determining appropriate concentration and time windows for preconditioning. This study investigated the brain protective effects with a single sevoflurane preconditioning at different concentrations and different time windows on MCAO rats. Methods: Adult Sprague-dawley rats were randomly assigned to 14 groups. The rats in the sevoflurane preconditioning group inhaled 0.5 MAC, 1.0 MAC, and 1.3 MAC sevoflurane, respectively for 3 h, and then MCAO models were established at 6 h, 12 h, 24 h, and 48 h. MCAO and sham groups underwent no preconditioning with sevoflurane. The neurological severity score, cerebral infarct volume and brain water content of the rats were measured 24 h after reperfusion. Results: After inhalation of 1.3 MAC sevoflurane for 3 h of preconditioning, the MCAO model was established after 24 h. This preconditioning improved the neurological severity score, reduce cerebral infarct volume and brain water content in MCAO rats. After inhalation of 1.0 MAC sevoflurane for 3 h of preconditioning, MCAO model established after 24 h reduced the cerebral infarct volume and brain water content of MCAO rats, but the neurological severity score showed no significant improvement, and no significant brain protective effects were observed at other concentrations and time windows. Conclusions: These results suggested that after inhalation of 1.3 MAC sevoflurane for 3 h of preconditioning, MCAO model established after 24 h demonstrated significant brain protective effects in MCAO rats. [ABSTRACT FROM AUTHOR]