Pyrogallol is a polyphenol that generates the superoxide anion. In this study, we investigated the influence of pyrogallol on human platelets. Our data showed that exposure of platelets to pyrogallol induced numerous manifestations of apoptosis including depolarization of mitochondrial inner membrane and release of cytochrome c from the mitochondria. Pyrogallol also induced downstream extra-mitochondrial apoptotic responses, including activation of caspase-3 and phosphatidylserine exposure on the outer leaflet of the plasma membrane. Addition of glutathione significantly rescued cells from pyrogallol- induced apoptosis, as evidenced by a decrease of all markers of apoptosis. Thus, pyrogallol appears to produce depletion of intracellular glutathione content in platelets, the main non-protein antioxidant in the cells. Furthermore, inhibition of γ-glutamyl transpeptidase, an enzyme that plays the main role in the cellular supply of glutathione, reverted the glutathione (GSH) protection over platelet apoptosis. Our results indicate that pyrogallol induces apoptosis by suppressing the natural anti-oxidation in human platelets.