The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307) phosphor-ylation, protein phosphatase 2A (PP2A) activity, and on tau phosphorylation. Specific Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein, and the phosphorylation levels of PP2A Y307 and tau at different sites, as well as PP2A activity were detected at different time points after siRNA transfection. Twelve hours after siRNA transfec-tion, the protein level of Src was dramatically decreased, with decreased PP2A Y307 phosphorylation. However, the total PP2A protein level was also decreased, together with a decreased PP2A activity. Tau was hyperpho-sphorylated at the Serl98/199/202 sites. Multiple factors may be involved in the cellular regulation of PP2A activ-ity. Inhibiting Src expression could induce inactivation of PP2A and tau hyperphosphorylation.