Objective: Adenosine leads to vasodilatation in most vascular beds however adenosine can induce vasoconstriction of the renal afferent arteriole of the mouse. Furthermore, the afferent arteriolar vasoconstrictor response is important for the tubuloglomerular feedback mechanism while the effect of adenosine on efferent arterioles is unclear. Methods: The effect of adenosine was investigated in perfused efferent arterioles isolated from mouse kidney and humane intra-renal arteries. Using RT-PCR with specific primers, the expression of adenosine receptors was also determined in mouse and human renal vasculature. Results: In perfused preconstricted efferent arterioles, adenosine applied extraluminally dose-dependently dilated efferent arterioles. This adenosine-induced vasodilatation was inhibited by the A2 adenosine receptor antagonist. Furthermore adenosine and an A2 adenosine receptor agonist dilated preconstricted human arteries. A1, A2a, A2b, and A3 adenosine receptors were expressed in microdissected mouse efferent arterioles and A2a adenosine receptors were observed in human intrarenal arteries. Conclusion: Adenosine has a direct effect on mouse efferent arterioles causing dilatation by activation of A2 adenosine receptors at concentrations compatible with activation of the A2b receptor subtype. Finally adenosine can dilate human intra-renal arteries through the A2a receptor subtype.