Adenosine is an endogenous vasodilator and is believed to play important roles in the regulation of coronary blood flow. Inward rectifier potassium (K_IR) channels have been selectively found in small resistance coronary arteries and cerebral arteries. We studied the effect of adenosine on the Ba²⁺-sensitive K_IR channels in the smooth muscle cells isolated from the small-diameter (≤100 μm) coronary arteries of humanely killed New Zealand White rabbit. Adenosine increased K_IR currents in concentration-dependent manner (EC50 = 9.4 ± 1.4 μM, maximum increase of 153%). The adenosine-induced stimulation of K_IR current was blocked by adenylate cyclase inhibitor, SQ22536 and was mimicked by adenylate cyclase activator, forskolin. The adenosine-induced increase of current was blocked by cyclic AMP-dependent protein kinase (PKA) inhibitors, KT5720 and Rp-8-CPT-cAMPs. The adenosine-induced stimulation was blocked by an A₃-selective antagonist MRS1334, while the antagonists of other subtypes (DPCPX for A₁, ZM241385 for A_2A, and alloxazine for A_2B) were all ineffective. Furthermore, an A₃-selective agonist, 2-Cl-IB-MECA induced increase of K_IR current. We also examined the effect of adenosine on coronary blood flow (CBF) rate by using the Langendorff-perfused heart. In the presence of glibenclamide to exclude the effects of ATP-sensitive K⁺ (K_ATP) channels, CBF was increased by adenosine (10 μM), which was blocked by the addition of Ba²⁺ (50 μM). Above results suggest that in rabbit coronary arteries, adenosine increases K_IR current via A₃ subtype in a PKA-dependent manner.