Aim To investigate the activity and expression of calcineurin(CaN) in the apoptosis of rat vascular smooth muscle cells(VSMC) under the stimulation of interferon gamma(IFN-γ)and CD40 ligand(CD40L),and the relationship between CaN and apoptosis of VSMC.Methods VSMC were obtained from SD rat and cultured in conditioned medium.Expression of CaN was measured by Western Blot and expression of CD40 and apoptosis of VSMC were examined by flow cytometry.Results The expression of CD40 in VSMC was clearly demonstrated.Activiation of VSMC by IFN-γ resulted in significant increase of expression of CD40 in VSMC(18.5%±0.2% vs 44.2%±2.4%).VSMC of control group showed low CaN activity(1.56±0.53 mmolPi/(g.h)),which was significantly enhanced by stimulation of IFN-γ,CD40L or combined stimulation of IFN-γ and CD40L respectively(6.48±1.09 mmolPi/(g.h),6.26±1.47 mmolPi/(g.h),11.70±2.73 mmolPi/(g.h),P<0.01),and so was the apoptosis of VSMC(P<0.01).The activity of CaN was significantly decreased after addition of FK506(2.74±0.30 mmolPi/(g.h),P<0.01).Conclusion The expression of CD40 was increased by the stimulation of IFN-γ.And combination of CD40-CD40L can increase the activity of CaN to induce the apoptosis of VSMC.