Hypertension is a major health problem globally necessitating exploration for new preventive and therapeutic tools. The community in North Western Ethiopia uses a local alcoholic beverage from Lupinus albus L. seed called â€œgebto arekeiâ€ for the treatment of hypertension. Although it has been extensively proven as an antihypertensive preparation, it lacks scientific evidence. Thus, the aim of this study was to investigate ex-vivo vasorelaxation activity and possible mechanisms of Lupinus albus L. distillated seed extract in isolated guinea pig thoracic aorta.rnVasorelaxation effects of different concentrations of extract (4-32Î¼g/ml) was investigated in isolated thoracic aorta strips of guinea pigs. Vasorelaxation response was evaluated by ex-vivo isometric tension recording method.rnThe extract induced vasorelaxation response in both endothelium intact and endothelium denuded strips as well as strips pre-incubated with NG nitro-L-arginine methyl ester and methylene blue in concentration-dependent manner. The extract showed synergistic activity when combined with sodium nitroprusside. Determination of calcium concentration responses revealed significant inhibition of contraction. The concentration that caused maximal relaxation and 50% maximal relaxation was found to be 4.74Î¼g/ml and 3.80Î¼g/ml respectively in epinephrine pre-contracted endothelium intact strips where as it was 21Î¼g/ml and 7.01Î¼g/ml in similar strips pre-contracted by potassium chloride.rnHence, popular usage of Lupinus albus L. seed preparation as a phytomedicine in the treatment of hypertension would be related to its effect through endothelial nitric oxide synthase-nitric oxide-cyclic guanosine monophosphate pathway and direct inhibitory effect on voltage dependent calcium channels. The findings shown that the preparation is endowed with vasorelaxation activity, providing evidence for its traditional use in the treatment of hypertension.