Objective To investigate the protective effect and the mechanism of isoflurane preconditioning on rat brain tissue suffering from rat liver ischemia-reperfusion injury. Methods 75 SD rats were randomly divided into five groups, sham group (S group); ischemia-reperfusion group (I/R group): liver ischemia for 60 min, reperfusion for 120 min; isoflurane preconditioning group (ISO group): 60 min before liver I/R,ISO pretreatment for 30 min; CsA+ISO group; CsA (MPTP specific blocker) 50 mg/kg intravenous injection, the same as ISO group after 30 min; CsA group: CsA 50 mg/kg intravenous injection. 30 min before I/R.The animals were killed 24 h after ischemia and their brain were excised for measurement of mitochondrial permeability transition pore (MPTP) and calcium content in mitochondria. The measurement of content of S-100β protein in serum before ischemia and 120min after reperfusion through the application of Elisa kit. Results The mitochondrial Ca²⁺ concentration of I/R group(287.32±26.17)was higher than that in S group(198.54±21.02)and the ISO group(209.74±29.49)(P< 0.05), and Ca²⁺ concentration of CsA+ISO group(267.31±37.52) was higher than the ISO group (P< 0.05); there was not statistical significance between I/R and CsA group(288.63±23.15)(P< 0.05).MPTP were more opened in I/R group(△S:1.73±0.24)than that in S group(△S:2.36±0.35)and ISO group(△S:2.11±0.32)(P< 0.05),but MPTP were more opened in CsA+ISO group than that in ISO group (P< 0.05). The content of S-100β protein in serum was significantly higher in I/R group than that in sham and ISO groups (P< 0.05),and the content of S-100β protein in serum was significantly higher in CsA+ISO group than in the ISO groups (P< 0.05). Conclusion The liver ischemia-reperfusion may injury the brain of the rat and isoflurane preconditioning can protect the brain on the rat. The reduce of mitochondria calcium overload and inhibition of MPTP opening are involved in the mechanism.