Introduction One of the most serious adverse effects of doxorubicin (DOX) chemotherapy is the development of cardiomyopathy. Here we sought to investigate whether exercise training would ameliorate structural cardiac damage after the development of DOX-induced cardiomyopathy. Methods 48 male Sprague Dawley rats (220-250 g) received intraperitoneal injections of DOX (1 mg.kg-1.day-1, total 10 mg.kg-1) or 0.9% saline (SAL). Four weeks after injections, they were further divided into exercise (EX) or sedentary (SED) groups. EX groups exercised on a treadmill (30 min.d-1, at 60% of maximal velocity, 5 d.wk-1, for 6 wk). Forty eight hours after the last exercise bout, rats were anesthetized with thiopental (50 mg.kg-1, i.p.), and the heart was removed after KCl intracardiac injection. Fragments of the left ventricle were fixed at 2.5% glutaraldehyde in a 0.1 M cacodylate buffer and post-fixed in 1% osmium tetroxide with 0.8% potassium. Thereafter, fragments were dehydrated in acetone and embedded in Epon. Semithin sections were cut and stained with toluidine blue and observed with a light microscope. Ultrathin sections were obtained from selected areas with ultramicrotome, counterstained with uranyl acetate and lead citrate, and examined with a Zeiss EM 906 transmission electron microscope at 80 Kv. All experimental procedures were approved by the Institutional Animal Care and Use Committee (CEA/051/2009). Results Before starting training, cardiac dysfunction was confirmed by echocardiography in DOX rats, which showed significant reduction of 24 ± 4% in shortening fraction, and enlarged end-diastolic and end-systolic diameters. An elevated mortality rate was observed in both DOX/groups, but it was significantly lower in DOX/EX (33%) than in DOX/SED (67%) assessed by log rank test (P<.05). Ultrastructural analysis of the heart showed myocardial damage in both DOX/SED and DOX/EX (Fig.1C and 1D) when compared to the SAL/SED and SAL/EX groups (Fig. 1A and 1B). These changes consisted of mitochondria damage with degeneration or loss of cristae and intramitochondrial vacuoles. Moreover, we observed an increase in the mitochondrial matrix caused by mitochondrial loss and intense disarray and fragmentation of myofilaments. Fig.1. Electron micrographs of cardiac specimens. A, saline/sedentary; B, saline/exercised; C, doxorubicin/sedentary; D, doxorubicin/exercise. Bars 2 µm. Conclusion The increased survival observed in the DOX/EX group cannot be attributed to an improved myocardial structure. We had previously reported that exercise training led to an improvement in vascular smooth muscle relaxation,1 and therefore we believe that despite the absence of changes in the heart structure, the reduced afterload could contribute to a reduced myocardial oxygen demand.