Glioma cells release glutamate during growth, which promotes proliferation and migration of itself and causes excitotoxicity to the surrounding neurons by Ca2+ influx through glutamate receptors. However, the role of glutamate and its receptors in the photodynamic therapy (PDT) on glioma cells is still unclear. Here we administered α-amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor (AMPAR) antagonist prior to PDT on C6 glioma cells. The changes of glutamate release, expression of AMPAR, apoptosis of C6 cells, and intracellular free calcium([Ca2+]i)were examined after PDT.We found that PDT increased extracellular glutamate and expression of AMPAR subunit GluR1 and GluR2, which might result in Ca2+ influx and apoptosis of C6 cells.When AMPAR antagonist was added, intracellular free calcium reduced and apoptosis rate of C6 cells decreased. These results indicate that PDT may lead to death of C6 glioma cells partly through glutamate and its receptors AMPAR, which induces Ca2+ influx and then cells apoptosis. This study allows us to further understand the effects and molecular mechanism of PDT on glioma.