Abstract: The objective of this work was to study the protective effect and mechanism of Terminalia chebula polyphenol extract(TCPE)on methamphetamine(METH)-induced cell injury in rat pheochromocytoma(PC12)cells. Methods:PC12 cells were divided into control group,model group(3 mmol/L METH)and TCPE-treated groups(25,50,100,200 μg/mL TCPE+3 mmol/L METH). After treatment,the following parameters were measured to detect cell responses which were cell viability,apoptosis,DNA damage,SOD and GSH-Px activities,MDA and ROS contents. Results:Compared with the control group,3 mmol/L METH significantly reduced the survival rate of PC12 cells(P<0.01),SOD and GSH-PX activity(P<0.05),significantly increased MDA content(P<0.05),apoptosis rate,ROS content and DNA damage(P<0.01). Compared with the model group,50~200 μg/mL of TCPE could significantly inhibit the decrease of survival rate and SOD activity of PC12 cells induced by METH(P<0.01),the decrease of GSH-PX activity(P<0.05),and the increase of apoptosis,DNA damage,intracellular MDA and ROS content induced by METH(P<0.01).Conclusion:TCPE has a significant protective effect on METH-induced PC12 cell injury,and its mechanism may be related to its inhibition of METH-induced oxidative stress and DNA damage.