The aim of this study is to investigate the neurotoxic effect and mechanism of 1-methyl-4-phenylpyridinium (MPP+) on PC12 cells. MTT assay was used to investigate cell viability, Western blotting assay was performed to observe the protein level and phosphorylation, and dual-luciferase assay was used to study the transactivation. The experiment showed that MPP+ could decrease cell viability significantly in a dose-dependent manner and could decrease BDNF protein level, depress the phosphorylation of ERK, and attenuate the phosphorylation and transactivation of CREB, which is one of transcription factors of BDNF, but did not affect the activity of CaMK II in PC12 cells. So MPP+ might decrease BDNF protein level through MAPK/ERK signal pathway.