Objective Increasing evidence suggests that oxidative stress may be implicated in the degeneration of dopaminergic neurons in Parkinsons disease (PD), and anti-oxidation has been shown to be effective in PD treatment.Myricetin has been reported to have the biological functions of anti-oxidation, anti-apoptosis, anti-inflammation and iron-chelation.The aim of the present study is to investigate the neuroprotective effect of myricetin on 1-methyl-4-phenylpyridinium (MPP+)-treated MES23.5 cells and the underlying mechanisms.Methods The cell viability was assayed by MTT assay.The production of intracellular reactive oxygen species (ROS), mitochondrial transmembrane potential (△Ψm) and caspase-3 activation were measured by flow cytometry.The mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) and c-Jun N-terminal kinase (JNK) activities were tested by Western blot analysis.Results The results showed that myricetin treatment significantly attenuated MPP+-induced cell loss and nuclear condensation.Further experiments demonstrated that myricetin could suppress the production of intracellular ROS, restore the △Ψm, increase Bcl-2/Bax ratio and decrease caspase-3 activation that induced by MPP+.Furthermore, we also showed myricetin decreased the phosphorylation of MKK4 and JNK caused by MPP+.Conclusion These results suggest that myricetin protected the MPP+-treated MES23.5 cells by anti-oxidation and inhibition of MKK4 and JNK activation.