The second messenger cyclic AMP (cAMP) plays a vital role in vascular physiology, including vasodilation of large blood vessels. We recently demonstrated cAMP activation of Epac-Rap1A and RhoA-ROCK-F-actin signaling in arteriolar derived smooth muscle cells to increase expression and cell surface translocation of functional α_2C-adrenoceptors (α_2C-ARs) that mediate vasoconstriction in small blood vessels (arterioles). The Ras-related small GTPAse Rap1A increased expression of α_2C-ARs and also increased translocation of perinuclear α_2C-ARs to intracellular F-actin and to the plasma membrane. This study examined the mechanism of translocation to better understand the role of these newly discovered mediators of blood flow control, potentially activated in peripheral vascular disorders. We utilized a yeast two-hybrid screen with human microVSM cDNA library and the α_2C-AR C-terminus to identify a novel interaction with the actin cross-linker, filamin-2. Yeast α-galactosidase assays, site-directed mutagenesis, and co-immunoprecipitation experiments in heterologous HEK 293 cells and in human microVSM demonstrated that α_2C-ARs, but not α_2A-AR subtype, interacted with filamin. In Rap1-stimulated human microVSMs, α_2C-ARs co-localized with filamin on intracellular filaments and at the plasma membrane. siRNA mediated knockdown of filamin-2 inhibited Rap1-induced redistribution of α_2C-ARs to the cell surface and inhibited receptor function. The studies suggest that cAMP-Rap1-Rho-ROCK signaling facilitates receptor translocation and function via phosphorylation of filamin-2 Ser-2113. Together, these studies extend our previous findings to show that functional rescue of α_2C-ARs is mediated through Rap1-filamin signaling. Perturbation of this signaling pathway may lead to alterations in α_2C-AR trafficking and physiological function.