Doxorubicin (Dox) is the most potent antitumor of wide spectrum. It is used only by developing cardiomyopathy threatening life. Cardiomyopathy is a disease of the heart muscle, categorized by abnormal wall thickness, chamber size and other functional contractile abnormalities. Pycnogenol (PYC) is an aqueous extract of the pine bark known for its content of bioactive flavonoids. The study aimed to examine the cardio-protective and therapeutic efficacy of Pycnogenol on doxorubicin brought cardiomyopathy. Fifty rats were divided into five equal groups as follow: G1 Control, G2 Cardiomyopathy group: doxorubicin dissolved in saline solution; 10 mg/kg; single i.p. injection. G3: healthy rats administered Pycnogenol treated with aqueous extract of pycnogenol (150mg /kg (b.w)/day) orally for five weeks, G4: Prophylactic group; rats received aqueous extract of Pycnogenol (150mg /kg (b.w)/day) orally, then received single injection of DOX (10 mg/kg b.w.i.p); G5: Cardio-therapeutic group; rats received single injection of DOX (10 mg/kg.i.p.) then, treated with aqueous extract of pycnogenol (150mg /kg (b.w)/day) orally. Blood samples were collected for biochemical measurements, hearts were excised for measurement of cardiac tissue oxidative stress and histological examination. Current evidence revealed that, DOX induced cardiomyopathy that confirmed in several aspects such as increasing TC, TG, and LDL-c with a reduction in HDL-c as compared to control group, it also decreased levels of oxidative stress parameters in cardiac tissues GSH and TAC and elevated NO and MDA levels. In the same way, DOX disturbs myocardial marker levels (CTnt, Acl, Ac.P, CRP, LDH). Pycnogenol treatment either as prophylactic or therapeutic improved lipid profile, oxidative stress markers and decreased myocardial marker injury. Furthermore, histological findings confirmed the biochemical aspects. Protection was more apparent in therapeutic group rather than in prophylactic group. Results affirmed that Pycnogenol aqueous extract protected against DOX induced cardiomyopathy in experimental rats.