Aim To investigate the effects of 12-O-tetradecanoyl phorbol 13-acetate(TPA) on the apoptosis of vascular smooth muscle cells,and the mechanisms underlying it.Methods The smooth muscle cells(SMC) A10 were passed down to logarithmic phase,then were incubated with TPA in different concentrations and at different time points.The apoptotic cells were detected by TUNEL assay.The protein levels of protein kinase B(Akt) and its downstream targets such as Foxos3a,GSK3β were analyzed by Western blot.Results TPA has a marked effect on apoptosis in SMC through inhibition of Akt activation.Moreover,TPA-induced inactivation of Akt was accompanied with the amount of time or dose that SMC was exposed to.Furthermore,protein kinase C(PKC) signaling pathway was involved in the inactivation of Akt in response to TPA treatment.Conclusions TPA induces apoptosis of SMC through inactivation of Akt,which is mediated by PKC signaling.