To study the effect of manganese with different valences to apoptosis, human neuroblastoma cell line (SH-SY5Y) has been chosen to study the induction of Mn2+ and Mn3+ on apoptosis and the content of dopamine in vitro. The results showed that both Mn2+ and Mn3+ induced a time-dependent decrease in SH-SY5Y cell viability, as determined by MMT assay. In the meantime, apoptosis was inducted by flow cytometer analysis (FCAS) after culture of Mn2+ or Mn3+ (0.5-2 mmol/L) with SH-SY5Y cell for 24-72 h. The ultrastructural changes of apoptosis such as nuclear chromosome condensation, was seen by transmission electron microscope. In addition, DA content was decreased by measured with HPLC. The major path of cell death induced by Mn2+ and Mn3+ may be due to apoptosis. Both Mn2+ and Mn3+ could induce the reduction of DA content. All these results suggest that Mn3+ appeared to be more cytotoxic than Mn2+.