This work aimed to study the cardioprotective effects of human brainnatriuretic peptide (BNP [Nesiritide]) and β-Blocker (Carvedilol) againstisoprenaline (ISP) induced acute heart failure (AHF) in the rats. 63 albino rats were intoxicated with isoprenaline (ISP, 85mg/kg SC for 2 consecutive days) to induce AHF then treated with SC BNP (10μg /kg, twice daily) or intragastric β-Blocker (5 mg/kg /day) from the third dayafter ISP injection for the next 10 days or treated with half dose-combination ofboth drugs or injected with SC saline (0.9 %, 1 ml/Kg twice daily) from thethird day after ISP injection for the next 10 days. Other 17 rats were served asnormal control rats and injected with SC saline (0.9 %, 1 ml/Kg twice daily).Hearts were excised from the experimental animals for assessment of cardiacfunction, BNP gene expression, malondialdehyde (MDA) and histopathologicalabnormalities. Blood was withdrawn for measurement of plasma cardiacbiomarkers (Pro-BNP, aldosterone, adrenomedullin, cardiac troponin I (cTn-I)and hs-CRP). ISP cardiotoxicity resulted in AHF characterized by depressedcardiac functions associated with neurohormonal changes and elevated cardiacbiomarkers that were confirmed by the histopathological examination.Treatment with BNP and/or β-Blocker showed marked limitation of ISPcardiotoxicity while the combined therapy of both drugs showed synergisticeffects.The use of BNP and/or β-Blocker in the treatment ofAHF significantly offered cardioprotection against ISP cardiotoxicity.Nevertheless, there were no significant differences were found between groupstreated by each drug alone but the low dose combined therapy showedsynergistic effects.