Zinc ion has both essential and toxic effects on mammalian cells. The results demonstrated that the ability of zinc to act as an inducer of apoptosis in C6 glial cells. Incubation with 0.2 mM ZnCl₂ caused cell death that was characterized as apoptosis by internucleosomal DNA fragmentation, formation of apoptotic bodies, nuclear fragmentation and breakdown of the mitochondrial membrane potential. ZnCl₂-induced apoptosis of C6 glial cells was prevented by the addition of Sibjeondaebo-Tang and antioxidants including reduced glutathione, N-acetyl-L-cysteine. We further confirmed that ZnCl₂ decreased the intracellular levels of GSH as well as generation of H₂O₂ in C6 glial cells. In 2D-electrophoresis, computer-assisted comparative analysis of the respective silver stained spot patterns revealed 3 groups with strongly decreased intensity by ZnCl₂. Whereas, 3 groups with increasing intensity were recovered by Sibjeondaebo-Tang. These results suggest that Sibjeondaebo-Tang may function as an antioxidant against free radicals and be applicable to the treatment of brain cells against oxidative stress.