Moderate elevation of extracellular K+ ([K+]out) may cause relaxation of some arteries. Local elevation of [K+]out between endothelial and smooth muscle cells may be induced by endothelial-derived hyperpolarizing factor (EDHF). Also, an increase of [K+]out in tissue can happen during intensive organ metabolism. Activation of inward rectifier potassium channels (KIR) may contribute to the K+-induced relaxation because their hyperpolarizing influence increases during elevation of [K+]out. However, the contribution of KIR in vascular tone regulation may vary in different organs. In this regard, we studied the role of KIR in K+-induced relaxation in two functionally different vascular regions of rat distal hindlimb: arteries of skin and skeletal muscle. We used saphenous artery, ventral branch of saphenous artery and arteries of lateral and medial heads of gastrocnemius muscle (sural artery) from male Wistar rats (277-440 g). Artery segments were placed in isometric myograph (DMT A/S). During preconstriction we registered relaxation induced by: (1) acetylcholine (range from 10-8 to 10-5 M), (2) elevation of [K+]out (from 4,5 mM to 19,5 mM). In order to identify EDHF component of acetylcholine-induced relaxation we inhibited NO-synthase (L-NNA, 10-4 M) and cyclooxygenase (indomethacin, 10-5 M). The contribution of KIR in relaxatory mechanisms was defined by KIR-blocker (Ba2+, 3*10-5 M). Ouabain (10-3 M) was used as a blocker of Na+/K+-ATPase. Expression of KIR mRNA (subtypes KIR2.1, KIR2.2, KIR2.3, KIR2.4) was studied by qPCR. GAPDH and 18S were used as reference genes. EDHF contribution to acetylcholine-induced relaxation was the most prominent in sural arteries, while in the skin arteries EDHF component of acetylcholine-induced relaxation was almost absent. In the sural arteries in the presence of Ba2+ EDHF-induced relaxation significantly diminished; combined inhibition of KIR and Na+/K+-ATPase completely suppressed EDHF-induced relaxation. The K+-induced relaxation of the skin arteries was mild, meanwhile, the sural arteries relaxed almost completely (80-100%) at rise of [K+]out. KIR blockade led to a reduction of sural arteries relaxation, especially at high [K+]out concentrations (from 9 to 19,5 mM). Combined inhibition of KIR and Na+/K+-ATPase completely suppressed K+-induced relaxation. KIR2.2 were the most abundant among the KIR subtypes. Its expression was the highest in the sural arteries. Our results demonstrate that the skeletal muscle arteries incline more to relax at the general and at the local elevation of [K+]out, than the skin arteries. In both cases K+-induced relaxation diminished during a KIR blockade. All in all, KIR are more essential for the K+-induced relaxation of the skeletal muscle arteries, than of the skin arteries, as it corresponds with the functions of these arteries in the organism.