Bee venom (BV) has been used in Oriental medicine to treat inflammatory diseases, such as tendonitis, bursitis, and rheumatoid arthritis, despite the sensitivity of the victims and toxicity of the venom. This study examined the mechanisms for the effects of BV on the cardiovascular system in rats. The arterial pressure and heart rate (HR) were measured in anesthetized rats. In addition, the left ventricular development pressure (LVDP) and total magnesium efflux ([Mg]e) in isolated perfused hearts, the vascular tonic responses in the isolated aorta, and the blood ionic and biochemical changes were determined simultaneously. In the anesthetized rats, the mean arterial pressure, systolic pressure, and pulse pressure were reduced by BV in a dose-dependent manner, even though the HR was increased. BV had no effects on the relaxation of phenylephrine- or KCl-induced contraction of the aortic rings. In the isolated hearts, BV generated a reversible decrease in the LVDP and velocity with changes in pressure, which were accompanied by increases in the HR and [Mg]e. BV increased the plasma ionized and total magnesium concentrations, and decreased the total magnesium level in the red blood cells. The ratio of ionized calcium/ionized magnesium was also decreased by the BV treatment. BV caused a detectable increase in blood creatine kinase, glutamic oxaloacetic transaminase, and lactic dehydrogenase, as well as a decrease in the blood total protein albumin and globulin levels. These results suggest that BV induces cardiovascular depression by decreasing the cardiac pressure and increasing the ionized magnesium concentration in the blood.