Abstract: Objective To investigate the protective effect of grape seed proanthocyanidin extract(GSPE) on cisplatin(cDDP)-induced testicular toxicity in mouse testes sertoli cells TM4 and its possible mechanism. Methods GSPE and/or cDDP were administered to TM4 cells. The survival rate of the cells was evaluated by MTT assay. Malondialdehyde(MDA) content was measured by thiobarbituric acid way. Nitric oxide(NO) and nitricoxide synthase(NOS) content were detected by nitrate reductase way. Superoxide dismutase(SOD) content was examined by xanthine oxidase method. Glutathione(GSH) and glutathione peroxidase(GSH-Px) content were determined by nitrobenzoic acid method. In addition, morphological changes of the cells were observed by microscopy. Results GSPE could significantly enhance the survival rate of TM4 cells, inhibit the toxic effect of cDDP on TM4 cells, and decrease the content of MDA, NO, NOS, while SOD, GSH, GSH-Px depletion were slowed. GSPE had a significant inhibitory effect to decrease the content of antioxidase and increase the level of lipid peroxide on cDDP-induced TM4 cells (P<0.01). Conclusion The cDDP-induced damage in intracellular findings of TM4 cells could be remarkably reversed by GSPE, which may be related with the antioxidant potential of GSPE.