Abstract—The role of vascular smooth muscle inward rectifier K+(KIR) channels in the mechanisms underlying vasodilation is still unclear. The hypothesis that KIRchannels are involved in sodium nitroprusside (SNP)-induced dilation of rat-tail small arteries was tested. SNP relaxed tail small arteries with an EC50of 2.6×10−8mol/L. Endothelium removal did not attenuate this effect. Vessel pretreatment with hydroxocobalamin, a nitric oxide (NO) scavenger, but not with rhodanese and sodium thiosulfate, inactivators of cyanide (CN), abolished the SNP effect. Vessel pretreatment with 10−5mol/L Ba2+, a specific blocker of KIRchannels at micromolar concentrations, reduced the SNP effect. Low concentrations of K+dilated the vessels; this effect was attenuated largely after pretreatment with 3×10−5mol/L Ba2+. In freshly isolated smooth muscle cells, a barium-sensitive current was observed at potentials negative to the potassium equilibrium potential. Application of 10−4mol/L SNP increased the barium-sensitive current 1.79±0.23-fold at −100 mV and hyperpolarized the membrane potential by 8.6±0.5 mV. In tissue from freshly dissected vessels, transcripts for KIR2.1 and 2.2, but not for KIR2.3 and 2.4, were found. However, only KIR2.1 antibodies immunostained the tunica media of the vessel. These data suggest that vascular smooth muscle KIR2.1 channels are involved in the SNP-induced dilation of rat-tail small arteries.