Previously, we found that exposure to a 50-Hz magnetic field (MF) could induce human amniotic epithelial (FL) cell proliferation and sphingosine kinase 1 (SK1) activation, but the mechanism was not clearly understood. In the present study, the possible signaling pathways which were involved in SK1 activation induced by 50-Hz MF exposure were investigated. Results showed that MF exposure increased intracellular Ca 2þ which was dependent on the L-type calcium channel, and induced Ca 2þdependent phosphorylation of extracellular regulated protein kinase (ERK), SK1, and protein kinase C a (PKCa). Also, treatment with U0126, an inhibitor of ERK, could block MF-induced SK1 phosphorylation, but had no effect on PKCa phosphorylation. Also, the inhibitor of PKCa, G€ o6976, had no effect on MF-induced SK1 activation in FL cells. In addition, the activation of ERK and PKCa could be abolished by SKI II, the inhibitor of SK1. In conclusion, the intracellular Ca 2þ mediated the 50-Hz MF-induced SK1 activation which enhanced PKCa phosphorylation, and there might be a feedback mechanism between SK1 and ERK activation in responding to MF exposure in FL cells.