Abstract: This study was aimed to investigate mechanisms underlying the blood pressure lowering effect of the crude extract of Azadirachta indica (Ai.Cr) and its aqueous (Ai.Aq) and ethylacetate (Ai.EtAc) fractions. In normotensive anesthetized rats, Ai.Cr (1-30 mg kg^-1) caused a dose-dependent fall in arterial pressure, Ai.Aq being more effective. In isolated rabbit aorta ring preparations, Ai.Cr inhibited phenylephrine (1 μM) and high K⁺ (80 mM) pre-contractions, with slightly higher potency against phenylephrine while Ai.EtAc was more potent against K⁺, similar to verapamil. The aqueous fraction was equipotent against both pre-contractions. Pre-treatment of aortic rings with Ai.Cr and both of its fractions shifted the Ca⁺⁺ concentration-response curves to the right, similar to verapamil. In isolated rat aorta preparations, Ai.Cr and Ai.Aq exhibited endothelium-dependent _L-NAME and atropine-sensitive and Ai.EtAc endothelium-independent vasorelaxation, similar to verapamil. Against high K⁺-pre-contractions, crude extract and Ai.EtAc were comparable in potency while, Ai.Aq was less potent. In isolated guinea-pig atrial preparations, crude extract and Ai.Aq were equipotent against both force and rate of contractions while Ai.EtAc was more potent against the rate. These data show that the crude extract of A. indica possesses vasodilator effect, mediated through Ca⁺⁺ channel blockade and NO-dependent atropine-sensitive pathways along with cardiac depressant activity which possibly explain its blood pressure lowering effect.