Flavonoids are present in many plants and isoflavone 3, 3′, 4′, 5, 7-penta-hydroxyflavone (quercetin) is one of the widely distributed and well known bioflavonoids, which produce a number of biological effects including apoptosis, protein kinase C and lypoxygenase inhibition, and superoxide dismutase-like activation. Considering that protein kinase C and related reactive oxygen species (ROS) overproduction are involved in a number of vascular abnormalities, it seems very relevant to address the possibility that quercetin may be therapeutically beneficial under oxidative stress. It was shown in preliminary studies (1, 2) that free quercetin and quercetin-filled phosphatidylcholine liposomes (PCL-Q) effectively normalize endothelium-dependent vascular smooth muscle (SM) relaxation and outward macroscopic currents carried by large conductance Ca2+ -dependent K+ channels (Maxi-K) in rat thoracic aorta smooth muscle (SM) cells inhibited under ionized irradiation but underlying mechanisms remain unclear.The aim of this study was thus to investigate the effects of-PCL-Q on single Maxi-K channel activity in mouse ileac myocytes. Cells were isolated from mouse (male, 2 month old) ileum longitudinal SM by enzymatic digestion (1 mg/ml, collagenase 1A, 1 mg/ml, soybean trypsin inhibitor, 1 mg/ml, bovine serum albumin, 18 min at 36.5 0C). Single Maxi-K channel currents were recorded in the cell-attached configuration using hyper-K+ (130 mM) external solution in the bath to bring the resting membrane potential to about 0 mV and normal physiological salt solution containing 6 mM K+ in the pipette. Channel activity was expressed as NPo. Bath application of PCL-Q (3 μg/ml by quercetin) increased single MaxiK channel activity about threefold, from 0.010±0.003 to 0.034±0.004 (p<0.05, n=4), whereas there was only a non-significant increase in single channel conductance from138 to 146 pS. In the presence of PCL-Q multiple simultaneous channel openings were observed, with up to 8 active channels in a patch. Surprisingly, testing the PCL-Q we have also found that “empty” phosphatidylcholine liposomes (PCL, 100 μg/ml) also produced some channel activation, although it was less potent compared to PCL-Q. Thus, PCL increased NPo from 0.010±0.003 to 0.019±0.003, p<0.05, n=4, and did not affect single channel conductance (139 pS). We conclude that PCL-Q as well as PCL alone activate SM cell Maxi-K channels, mainly by increasing channel open probability. While incorporation of the liposomes into the plasma membrane, by altering channel’s phospholipids environment, may directly activate Maxi-K channels, the additive action of quercetin may be due to its well known inhibition of protein kinase C.