Objectives: Nigella sativa also known as Kalonji, used in ethnomedicine for treatment of various cardiovascular disorders. current study is aimed to evaluate cardioprotective potential of aqueous extract of Nigella sativa (AENS) against Doxorubicin (DOX) induced cardiotoxicity. Methods: Study was conducted in which 30 Wister albino rats were divided in 05 groups,06 rats in each group. Group I- Serve as control group received 2ml/kg body weight normal saline per os (p.o.) for 21 days, Group-II received pellet diet along with tap water as required for 21 days and injection DOX 20mg/kg was administered intraperitoneally (i. p.) on 21st day, Group III and Group IV- AENS 250+500mg/kg/day+ Injection DOX 20mg/kg i.p. on 21st day. Group V- Carvedilol 30 mg/kg/day p.o. for 21 days followed by Injection DOX 20 mg/kg i. p. single dose on 21st day, then all animals were anaesthetized by administering Ketamine and Diazepam i.p. cardioprotective potential of graded doses of AENS was evaluated by measuring serum level of CK-MB, LDH, SGOT, SGPT. After scarification of animal’s histopathological examination (HPE) of heart was performed. Data were appropriately organized and analyzed by using ANOVA and Post Hoc test. Results: Cardiac biomarkers CK-MB, LDH, SGOT, SGPT were raised remarkably in groups treated with DOX. AENS administered group revealed remarkable limitation in rise of CK-MB, LDH, SGOT, SGPT (p<0.001) in a dose dependent manner following administration of DOX which were comparable to the group treated with standard cardioprotective drug Carvedilol. histopathological changes were also corelated cardioprotective potential of Nigella sativa. Conclusion: Graded doses of AENS revealed significant cardioprotective potential against DOX induced cardiotoxicity.