Objective To investigate the brain protective effects of isoflurane preconditioning for local cerebral is-chemia adult rat model by detecting HIF-1α, HO-1 and Bcl-2 expression level. Methods 84 two-month old Spra-gue-Dawley male rats were randomly divided into sham group, ischemia-reperfusion group ( MCAO group) and isoflurance preconditioning group (ISO group). ISO group was exposed to isoflurane for 30 min and then underwent a 90 min middle cerebral arterial occlusion (MCAO), while MCAO group underwent MCAO only. At 24 h after reperfusion all the groups were investigated by modified neurological severity score for neurological deficits, TTC staining for infarct percentage. Cerebral cortices were harvested for HIF-1α, HO-1 and Bcl-2 protein expression level detection at 6 h, 24 h and 72 h after reperfusion using RT-PCR and western blot. Results The mNSS score and infarct percentage in ISO group decreased significantly compared with those of MCAO group at 24 h after reper-fusion(P < 0. 05). Compared with the MCAO group, ISO group had significantly up-regulated protein levels of HIF-1α, HO-1 and Bcl-2 at 6 h and 24 h after reperfusion(P < 0. 05). There was no difference between ISO group and MCAO group for 3 gene expression at 72 h(P > 0. 05). Conclusion Isoflurane preconditioning plays short-term cerebral protective effect through the up regulation of HIF-1α, HO-1 and Bcl-2 gene expression.