Doxorubicin (DOX) is a chemotherapeutic agent from anthracycline family used in the treatment of different neoplasms, however, it has a cardiotoxic side effect. The mean goal was to evaluate the pequi shell ethanolic extract (PSEE) effect on the activity of antioxidant enzyme glutathione reductase (GSH-Rd) in rats with doxorubicin-induced cardiotoxicity. Wistar rats were distributed in six groups of five animals each, with 1 ml of physiological solution applied in rats of sham group (GS); 16 mg/kg of DOX in animals of control group (GC); 16 mg/kg of DOX and 300 mg/kg of PSEE for 17 days in rats of G1; 16 mg/kg of DOX and 600 mg/kg of PSEE for 17 days in animals of G2; 16 mg/kg of DOX and 300 mg/kg of PSEE from the seventh day, for 10 days in rats of G3; and 16 mg/kg of DOX and 600 mg/kg of PSEE from the seventh day, for 10 days in animals of G4. The DOX and the physiological solution were applied on the 14th day after experiment start. It was quantified by spectrophotometry. At the dose of 300 mg/kg for 17 days the PSEE has increased the enzymatic capacity of GSH-Rd. It was concluded that PSEE at the dose of 300 mg/kg for 17 days increase the activity of the GSH-Rd enzyme, which may reflect positively along the deleterious effects of DOX in the myocardium of rats.