The water extract of Dohongsamul-tang(DHSMT)has been traditionally used for treatment of ischemic heart in oriental medicine. However, little is known about the mechanism by which the water extract of DHSMT rescues cells from these damages. Therefore, this study was designed to evaluate the protective effects of DHSMT on zinc-mediated cytotoxicity in H9c2 cardiomyoblast cells. This study demonstrates that treatment of H9c2 cells with zinc caused a decrease in cell viability in a dose dependent manner and a chromatin condensation. Zinc induced the cleavage of poly(ADP-ribose) polymerase (PARP). In addition, zinc induced the decrease of Bcl-2, as well as increase of Bak expression and mitochondrial dysfunction. Zinc-induced H9c2 cell death was remarkably prevented by the pretreatment of DHSMT with consistent suppression of the cleavage of poly(ADP-ribose) polymerase (PARP), mitochondrial dysfunction and the expression of Bak and Bcl-2. Taken together, the results suggest that zinc induced severe cell death in H9c2 cardiomyoblast cells via intracellular GSH(reduced glutathione) depletion and the protective effects of DHSMT against oxidative injuries may be achieved through modulation of mitochondrial dysfunction and scavenging of ROS(reactive oxygen species).