In order to evaluate the functional role of P-glycoprotein (P-gp) in cerebral ischemia, both multidrug resistance 1a knockout (KO) mice and wild-type mice were subjected to transient focal ischemia under a constant body and brain temperature about 37°C. The results showed that the volume of brain infarction induced by middle cerebral artery occlusion in KO mice was significantly smaller than that seen in wild-type mice, although there were no significant differences in cerebral blood flow, physiological data and on anatomical analysis of cerebrovasculature between both groups. We suggest that multidrug resistance 1a P-gp plays a role for adjusting the expressions of endogenous neuronal cell modulating substances, such as cytokines, neuronal peptides, and others, in the brain, which is consistent with a previous paper (Bobrov et al. Neurosci Lett 24: 6–11, 2008).