The aim of our study was to determine if strain (S) and strain rate (SR) imaging are more sensitive indices with respect to standard echocardiographic parameters to assess cardiac function in an experimental model of doxorubicin (DOX)-induced cardiomyopathy. DOX was administered intraperitoneally 4x/wk at the dose of 1.25 mg/kg/d over four weeks in Wistar rats (n = 26). Other 14 Wistar rats were used as controls. Echocardiographic studies were performed before DOX treatment (baseline), after two and four weeks of treatment. At two and four weeks of DOX treatment, rat hearts were collected for histologic analysis. After two weeks of DOX treatment, there were no significant changes in standard echocardiographic parameters and in myocardial velocities, but after four weeks of treatment, ejection fraction significantly decreased and left ventricle dimensions significantly increased. Also, myocardial velocities were significantly reduced after four weeks of treatment. Conversely, S and SR values changed significantly already after two weeks of treatment. At baseline, S and SR values were 27 +/- 7% and 7.4 +/- 1.7, respectively, and they significantly decreased to 12 +/- 6% (p < 0.0001) and 6 +/- 1.5 (p < 0.005) at two weeks of treatment. These changes were also significant compared with control rat parameters (p < 0.001). At four weeks of DOX treatment, a progressive worsening occurred. Strain and SR further significantly decreased to 10 +/- 4% (p < 0.0001 vs. baseline) and 4.6 +/- 1.6 (p < 0.0001 vs. baseline), respectively. These changes were supported by histologic findings. Indeed, damage in myocardial tissue was demonstrated by histology already after two weeks of DOX treatment, with a damage progression after four weeks of treatment. Our data demonstrate that S and SR imaging are more sensitive indices in identifying early myocardial systolic changes induced by DOX than standard echocardiographic parameters and myocardial velocities. We believe that our model will be very supportive to further assess these new diagnostic strategies to provide a precocious diagnosis of LV dysfunction with a unique opportunity to initiate preventive cardioactive therapy. (E-mail: giodisal@yahoo.it).