Background: Doxorubicin (DOX) is a potent chemotherapeutic drug that was widely used for the treatment of various types of cancer. It produces free radicals which result in extreme dose-limiting cardiotoxicity. Objective: the present study aimed to investigate the potential cardioprotective effect of exogenous NADPH, against doxorubicin-induced cardiotoxicity in albino rats. Material and Methods: 36 rats were divided into five groups: negative control (group I), positive solvent control (group II), which were subdivided into subgroup IIa (saline): they received (0.9% NaCl) (solvent of Doxorubicin), and subgroup IIb (modified saline) (solvent of exogenous NADPH): they received modified saline with PH: 8 (normal saline +10% NaOH). Group III (exogenous NADPH): the given dose was (8 mg/kg/day) iv/day for 7 days. Group IV (Doxorubicin): a single dose was (25 mg/kg), and it was given i.p. on the 7th day. Group V (Doxorubicin + exogenous NADPH): rats received a combination of Doxorubicin given in a single dose (25 mg/kg) i.p. on the 7th day and exogenous NADPH given in a dose (8mg/kg/day); iv/day for 7 days.