Introduction and Objective.High blood pressure is an important risk factor for heart-related disease. Combining dietary adjustments with standard drugs in the therapy of heart diseases have gained attention. Genistein, a soy isoflavone, has many biological effects but its role in blood pressure is inconclusive. The aim of the study was to investigate the effect of genistein on blood pressure in normotensive rats pre-treated with standard drugs. Materials and method. Twenty healthy adult male Sprague Dawley rats (body weight 160-180g) were administered with genistein, and SBP, DBP, PP, MABP and HR were recorded. Subsequently, the rats (5 each) were treated with Indomethacin, a non-steroidal, anti-inflammatory and a cyclooxygenase (COX-2) enzyme inhibitor (5 mg/kg subcutaneously), methylene blue,an inhibitor of nitric oxide synthase and guanylate cyclase (7.5 mg/kg, by infusion), nifedipine,a calcium channel blocker (0.75 mg/kg intravenously), and tetraethylammonium, a voltage-gated K+ channels blocker (60 mg/kg intravenously). Genistein was administered intravenously in graded doses after the administration of these blockers. SPB, DBP, PP and MABP were significantly increased following genistein administration only, as well as in the methylene blue and tetraethylammonium groups each. Results. Higher doses of genistein significantly decreased SBP, DBP and PP after indomethacin treatment. Falling DBP and MABP were reversed in the nifedipine group. Conclusions. Results suggests that genistein elevates blood pressure in experimental normotensive male rats. This has implications for alternative therapy in the management of hypertension, and implications for blood pressure in cardiovascular related diseases