Doxorubicin (DOX) is an anthracycline antibiotic and a quinone-containing chemotherapeutic drug used for various types of solid and hematological cancers. However, it causes many toxic side effects, including cardiac, renal, hematological, and testicular. The current study investigated the ameliorative effect of n-acetylcysteine against DOX-induced cardiotoxicity in albino rats. Sixty rats were divided into six groups. Group (A): rats received food pellets and tap water ad libitum. Group (B): rats received NAC (400 mg/kg/p.o.) Every other day for 28 days. Group (C): rats received DOX (5 mg/kg, i.p.) for four weeks on days 1, 7, 14 and 21. Group (D): rats received NAC (400 mg/kg/p.o.) every other day one week earlier and then along with DOX (5 mg/kg/ i.p.) for the next four weeks on days 1, 7, 14 and 21). Group (E): rats received NAC (400 mg/kg/ p.o.) every other day started at the first day of the experiment till the end of the experiment and DOX (5 mg/kg/ i.p.) for four weeks on day 1, 7, 14 and 21. Group (F): rats received NAC (800 mg/kg, p.o.) every other day started at the first day of the experiment till the end of the experiment and DOX (5 mg/kg, i.p.) for four weeks on day 1, 7, 14 and 21. Results showed a significant increase in levels of LDH, CK-MB, CTn-I, and (MDA). Whilst, levels of (GSH) and (GSH-Px) were significantly decreased. Moreover, there were histopathological abnormalities in the cardiac tissue of DOX-treated rats. The study demonstrated that NAC has a cardioprotective effect on the damage induced by DOX, through inhibition of inflammation and oxidative stress. This effect was more pronounced in groups (D, E&F), as it produced a significant increase in GSH and GSH-Px levels, a significant decrease in MDA, LDH, CK-MB, and CTn-I.