Background: Diabetes mellitus is common in patients with hypertension ,also, hypertension is more frequent in the diabetics than in the non-diabetic individuals. Genetics, environment, hormones, and other pathophysiologic factors contribute to this relationship. Drug therapy of hypertension with diabetes has been surrounded by a controversy because concurrent administration of antihypertensive and anti-diabetic agents is a common trend. Objectives: This work was designed to study some interactions between gliclazide(anti-diabetic) and nebivolol (anti-hypertensive) in experimentally induced diabetic hypertensive albino rats Methods: 50 adult male albino rats were used. They were divided into the following groups: G1: Non diabetic normotensive control (CN), Other 40 rats were subjected to induction of type 2 DM and hypertension by streptozotocin (STZ), the diabetic -hypertensive rats were selected and divided into 4 groups: G2: diabetic-hypertensive (DH) control ,G3: DH gliclazide treated (5mg/kg/day) ,G4: nebivolol treated (10 mg/kg/day) , G 5: DH gliclazide & nebivolol treated . After 8 weeks treatment, the following parameters were estimated: fasting blood glucose (FBG), mean arterial blood pressure (MABP) , Serum insulin, nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA) , lipid profile in addition to the response of isolated aortic strips to noradrenaline before and after acetylcholine Results: Nebivolol, significantly (p<0.05) decreased the elevated FBG,MABP,MDA and increased serum NO and SOD activity and improved NO dependent vasorelaxation response of aorta when compared with G2 group. Also, it significantly decreased LDL, TC. Furthermore nebivolol improved these parameters when administrated with gliclazide more than nebivolol alone. Conclusion: concurrent administration of nebivolol and gliclazide, improved many metabolic parameters, oxidative stress and vascular reactivity more than when each drug was administrated alone in experimentally induced diabetic hypertensive rats.