Urea is critical to the urinary concentrating mechanism and to the regulation of water balance. Vasopressin, through cAMP, stimulates urea transport across perfused rat terminal inner medullary collecting ducts (IMCD) by increasing UT‐A1 phosphorylation and membrane accumulation. Cyclic AMP is known to act through protein kinase A (PKA); however, it can also activate Epac (exchange protein activated by cAMP). We tested whether Epac is involved in regulation of urea transport and UT‐A1 transporter activity in rat IMCD. Functional analysis showed that the Epac activator, Sp‐8‐pCPT‐2 O‐Me‐cAMPS, significantly increased urea permeability in isolated, perfused rat terminal IMCDs by 29%. Incubation of rat IMCD suspensions with the Epac activator significantly increased UT‐A1 in the plasma membrane (biotinylated UT‐A1) and UT‐A1 phosphorylation. To further explore the signaling pathway, we tested whether forskolin could stimulate ERK 1/2 phosphorylation. Forskolin increased ERK 1/2 phosphorylation 25%; this increase was not inhibited by a PKA inhibitor, H‐89, indicating that ERK 1/2 phosphorylation was through Epac. The MEK 1/2 inhibitor, U0126, inhibited forskolin‐stimulated UT‐A1 phosphorylation. We conclude that activation of Epac increases urea transport, UT‐A1 phosphorylation, and UT‐A1 plasma membrane accumulation. The increase in UT‐A1 phosphorylation is mediated by the MEK‐ERK pathway.