The comparative study of cardio protective activity of nebivolol, carvedilol and metoprolol was carried out on doxorubicin-induced cardiac toxicity in rats. The degree of protection was assessed both in vivo by short axis echocardiography measuring ejection fraction (EF), fractional shortening (FS), left ventricular systolic diameter (LVSD) and left ventricular diastolic diameter (LVDD) and in vitro by measuring the inotropic and the chronotropic responses to isoproterenol (3μM, 6μM, 12μM). Also histopathlogical study was done using Hematoxylin and Eosin as a basic stain and Toluidine blue for histopathological grading of cardiac tissue injure (0-3). The prophylactic treatments of the three drugs P.O was given daily for 12 days in a dose of 10mg/kg/day for nebivolol and carvedilol while metoprolol 30mg/kg/day simultaneously with doxorubicin injection 3 mg/kg intraprotineally every other day for 12 days. In conclusion this study revealed that there is a significant improvement of cardiac functions in rats treated with β-blockers and there is no significant difference between carvedilol and nebivolol whereas nebivolol has the best histopathological score for improvement cardiac toxicity.