Glial glutamate transporter 1 (GLT-1) plays a vital role in the induction of brain ischemic tolerance (BIT) by ischemic preconditioning (IPC). However, the mechanism still needs to be further explained. The aim of this study was to investigate whether peroxisome proliferator-activated receptor gamma (PPAR gamma) participates in regulating GLT-1 during the acquisition of BIT induced by IPC. Initially, cerebral IPC induced BIT and enhanced PPAR gamma and GLT-1 expression in the CA1 hippocampus in rats. The ratio of nuclear/cytoplasmic PPAR gamma was also increased. At the same time, the up-regulation of PPAR gamma expression in astrocytes in the CA1 hippocampus was revealed by double immunofluorescence for PPAR gamma and glial fibrillary acidic protein. Then, the mechanism by which PPAR gamma regulates GLT-1 was studied in rat cortical astrocyte-neuron cocultures. We found that IPC [45 min of oxygen glucose deprivation (OGD)] protected neuronal survival after lethal OGD (4 h of OGD), which usually leads to neuronal death. The activation of PPAR gamma occurred earlier than the up-regulation of GLT-1 in astrocytes after IPC, as determined by western blot and immunofluorescence. Moreover, the preadministration of the PPAR gamma antagonist T0070907 or PPAR gamma siRNA significantly attenuated GLT-1 up-regulation and the neuroprotective effects induced by IPC in vitro. Finally, the effect of the PPAR gamma antagonist on GLT-1 expression and BIT was verified in vivo. We observed that the preadministration of T0070907 by intracerebroventricular injection dose-dependently attenuated the up-regulation of GLT-1 and BIT induced by cerebral IPC in rats. In conclusion, PPAR gamma participates in regulating GLT-1 during the acquisition of BIT induced by IPC. Open science badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at . Open Science: This manuscript was awarded with the Open Materials Badge For more information see: