The role of cGMP‐dependent protein kinase (PKG) in the regulation of rat aortic vascular smooth muscle cells (VSMC) phenotype was examined using a transfected cell culture system. Repetitively passaged VSMC do not express PKG and exist in the synthetic phenotype. Transfection of PKG‐lα cDNA, or the active catalytic domain of PKG‐lα, resulted in the appearance of VSMC having a morphology consistent with the contractile phenotype. PKG‐expressing cells also contained markers for the contractile phenotype (for example, smooth muscle specific myosin heavy chain, calponin, α‐actin) and reduced levels of synthetic phenotype markers (osteopontin, thrombospondin). PKG‐transfected VSMC have also reduced the levels of fibroblast growth factor receptors 1 and 2, consistent with the establishment of a more contractile phenotype. The regulation of PKG expression in VSMC is largely undefined; however, continuous exposure of cultured bovine aortic smooth muscle cells with nitric oxide (NO)‐donor drugs or cyclic nucleotide analogues reduced the expression of PKG. These results suggest that PKG occupies a critical role in VSMC phenotype and that suppression of PKG expression during inflammation or injury promotes a more synthetic state of the VSMC.