Previous studies reported that oxidative stress was involved in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH).Up-regulation of transglutaminase 2 (TG2) by oxidative stress has been reported to play a crucial role in cell apoptosis.This study aimed to investigate whether TG2 expression is up-regulated after SAH and cysteamine, a chemical inhibitor of TG2, prevents post-SAH oxidative stress injury via its antioxidative and anti-apoptotic effects.Here we induced SAH by double-injection of autologous blood into the cistema magna and intraperitoneally applied cysteamine.We found that TG2 expression was is elevated in brain cortex after SAH.Cysteamine improved neurobehavioral deficits and attenuated brain edema and blood-brain barrier permeability after SAH.Cysteamine attenuated SAH-induced cortical apoptosis, reduced post-SAH elevated lactate dehydrogenase (LDH) and lipid peroxidation (MDA) activities and reactive oxygen species (ROS) level.Cysteamine increased the levels of tissue glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) enzymatic activities and the concentration of brain derived neurotrophic factor (BDNF) after SAH.Altogether, our data indicated that administration of cysteamine may ameliorate EBI and provide neuroprotection after SAH in rats.