Aim To research the cross regulation of cGMP-dependent protein kinase(PKG) and calcineurin(CaN) in vascular smooth muscle cells(SMC) proliferation. Methods Primary vascular SMC from rat aorta were used as the experimental model.Expression of CaN and PKG was assayed using immunoblotting.Cell growth was determined by MTT assay. Results The results showed that phenylephrine(PE)-induced expression and activity of CaN protein was reduced by S-nitroso-N-acetylpenicillamine(SNAP) and Sp-8-pCPT-cGMP,but increased by Rp-8-pCPT-cGMP.The OD ratio of PKG Iα mRNA expression in 0.5 mg/L cyclosporin A(CsA) group resembled control group while in 5 mg/L CsA group was significantly higher than control group(p<0.01).Although the result of 5 mg/L CsA+10 μmol/L PE group was lower than 5 mg/L CsA group(the expression of mRNA decreased 32.2%;the production of PKG Iα protein decreased 36.7%,p<0.01),but still higher than control group obviously(p<0.05).In SMC pretreated with CsA,absorbance of cells stimulated by PE decreased by 36.67%,but it could not be further altered by the additional treatment of SNAP,Sp-8-pCPT-cGMP and Rp-8-pCPT-cGMP. Conclusion PKG and CaN can cross-regulate in vascular smooth mucle cells proliferation.