Aim To explore the effects of N-acetylcysteine(NAC) on methamphetamine(METH) induced neurotoxicity of striatum in rat model and its mechanism.Methods NAC was administrated(ip) 30 min prior to METH injection to produce toxic rat model.Dihydrodichlorofluorescein diacetate was used to detect the level of reactive oxygen species(ROS),high performance liquid chromatography for the concentration of Dopamine(DA),meanwhile,TUNEL method was used to observe the neuron apoptosis.Results Pretreatment with NAC could decrease the level of ROS in rat striatum,prevent the loss of DA and decrease the TUNEL-positive neurons.Conclusion NAC could attenuate methamphetamine-induced neurotoxicity in rat striatum by blocking ROS production.