Macrovascular and microvascular diseases are currently the principal causes of morbidity and mortality in patients with diabetes mellitus. Abnormalities in vascular endothelial and smooth muscle cells (SMCs) function contribute to the vascular complications in diabetes. The aim of this study was to evaluate the effect of antioxidant quercetin enclosed in phosphatidylcholine liposomes (PCL-Q) on diabetic endothelial dysfunction and changes in total outward K+ current in SMCs at diabetes. Experimental design of the study comprised SM contractile recordings and whole-cell patch-clamp technique. Data are presented as mean ± SEM with n indicating the number of vascular preparations tested. Dilator responses to acetylcholine (Ach, 10-9 – 10-5 M) were expressed as a percentage of the maximum response produced by norepinephrine (10-6 M). The endothelial function was assessed in aortic rings isolated from streptozotocin-treated male Wistar rats (STZ, 65 mg/kg, intraperitoneal injection). Diabetes was verified by the presence of hyperglycaemia measured in blood. Glucose level was 30.7±0.9 mM, n=11, P<0.05 in month after STZ injection. Diabetic rats were treated with PCL-Q (15 mg/kg or 50 mg/kg) intravenously twice with 1 day interval. Animals were killed in 2 weeks by cervical dislocation following ketamine (45 mg/kg, i.p.) and xylazine (10 mg/kg, i.p.) anesthesia. The concentration-response curve to Ach in the aortic rings precontracted with norepinephrine (10-6 M) was significantly shifted to the right (EC50: 6.97±0.1, n=11, P<0.05 in diabetic animals vs. 7.59±0.08, n=7 in control) and maximum relaxation in control and diabetic rats were 96.5±3.05%, n=7 and 58.98±7.75% (n=11; P<0.05), respectively. Treatment with PCL-Q significantly improved endothelium-dependent Ach-induced relaxation in diabetic rats and the maximum relaxation increased to 90.16 ± 2.48 %, n=16; P>0.05 (EC50: 7.55±0.07 (n=16; P>0,05) for animals treated with 15 mg/kg PCL-Q and 94.1±1.89 %, n=16, P>0,05 (EC50: 7.55±0.13, n=16, P>0.05) for treated with 50 mg/kg PCL-Q. Whole-cell patch-clamp technique showed a reduction of total K+ outward current in SMCs of diabetic rats versus controls (peak density was 22.1±1.6 pA/pF, n=8, P<0.05 for diabetes vs. 70.8±8.3 pA/pF, n=6 for control). SMCs from animals treated with PCL-Q (50 mg/kg) showed significant increase in total K+ currents with peak density 54.8±4.9 pA/pF (n=8, P>0.05) while the treatment with 15 mg/kg PCL-Q showed no change in total K+ current (peak density was 26±2.8 pA/pF, n=7, P<0.05). In conclusion, quercetin-filled phosphatidylcholine liposomes significantly improve endothelium-dependent relaxation and restore total K+ outward current in rats with diabetes mellitus.