Objective The aim of the present study was to clarify the mechanism underlying glioma cell death upon oligomeric procyanidins (F2) exposure. Methods The cytotoxicity of F2 on U87 (human malignant glioblastoma cell line) and C6 (rat glioma cell line) cancer cells was evaluated, and changes of mitochondrial membrane potential (MMP) and production of reactive oxygen species (ROS) in drug-treated cells were monitored. Moreover, morphological changes associated with F2-induced cells death were examined. Results F2 induced a concentration-dependent increase in ROS production and decrease in MMP. Furthermore, pre-incubation with N-acetylcysteine (NAC) and rotenone (Rt), resulted in partial inhibition of F2-induced ROS generation and marked attenuation of cell death and the cytoplasmic vacuolization induced by F2. In addition, pretreatment with Rt markedly attenuated the MMP loss in F2-treated cells. However, pretreatment with NAC only markedly attenuated the MMP loss in F2-treated C6 cells. Conclusion The increase in ROS level is at least one of mechanisms associated with F2-induced glioma cell death as well as the cytoplasmic vacuolization formation that contribute to the cytotoxicity of F2 in glioma cells. Objective The aim of the present study was to clarify the mechanism underlying glioma cell death upon oligomeric procyanidins (F2) exposure. Methods The cytotoxicity of F2 on U87 (human malignant glioblastoma cell line) and C6 (rat glioma cell line) cancer cells was evaluated as , and changes of mitochondrial membrane potential (MMP) and production of reactive oxygen species (ROS) in drug-treated cells were monitored. Moreover, morphological changes associated with F2-induced cells were monitored. Results F2 induced a concentration-dependent increase in ROS production and decrease in MMP. Further, pre-incubation with N-acetylcysteine ​​(NAC) and rotenone (Rt), resulted in partial inhibition of F2-induced ROS generation and marked attenuation of cell death and the cytoplasmic vacuolization induced by F2. In However, pretreatment with Rt markedly attenuated the MMP loss in F2-treated cells. However, pretreatment with NAC only markedly attenuated the MMP loss in F2-treated C6 cells. C onclusion The increase in ROS level is at least one of the mechanisms associated with F2-induced glioma cell death as well as the cytoplasmic vacuolization formation that contribute to the cytotoxicity of F2 in glioma cells.