Diazepam, a peripheral-type benzodiazepine receptor ligand, is widely used as a therapeutic agent. On the other hand, peripheral-type benzodiazepines have been shown to induce apoptosis in different immune cell types. In this study, we examined the possible protective role of vitamin C in diazepam-induced apoptosis and evaluated the cellular content of glutathione during this process. Rat thymocytes were incubated for 24 hours with diazepam and increasing concentrations of vitamin C or with diazepam alone. The exposure to diazepam resulted in an increase in apoptotic cell death and decrease in glutathione content in rat thymocytes. Vitamin C was effective in ameliorating the effect of diazepam in rat thymocytes by decreasing the proportion of apoptotic cells and increasing the cellular content of glutathione. These results suggest that vitamin C reduced the diazepam-induced apoptosis in rat thymocytes by restoring the cellular content of glutathione, which may be useful in preventing the diazepam-induced immunosupression (Tab. 1, Fig. 1, Ref. 31).