Abstract: Objective To study the effect of methamphetamine (METH) exposure on S-nitrosylation of protein disulphide isomerase and the neurotoxicity of METH in PC12 cells. Methods PC12 cells were exposed to different concentrations of METH, and the cell viability was assessed using the cell-counting kit-8. PC12 cells exposed to METH in the presence of the NOS inhibitor N-nitro-L-arginine (L-NNA) were examined for cell viability and S-nitrosylation of protein disulphide isomerase using the biotin-switch method, and the changes in cell morphology were examined with HE staining. Results METH exposure obviously decreased the cell viability and increased S-nitrosylation of protein disulphide isomerase, and the effect of METH was obviously inhibited by L-NNA treatment. Conclusion METH can cause obvious neurotoxicity and promote S-nitrosylation of protein disulphide isomerase in PC12 cells.