AIMS: Anthracycline-induced cardiotoxicity has high incidence rates and causes significant mortality among cancer survivors. Damage to myocardial tissue leads to left ventricular (LV) dilation with systolic dysfunction, typically assessed through echocardiographic measurement of LV ejection fraction (LVEF) and volumes. Early detection is crucial for improving patient outcomes. We aimed to evaluate cardiotoxicity progression and diagnostic performance of different echocardiographic modalities in an animal model. METHODS AND RESULTS: Female Sprague Dawley rats received either intravenous doxorubicin (DOX) injections weekly for 8 weeks (2 mg/kg/week) or saline (control). Transthoracic LV echocardiography was performed before treatment and at 4, 6, and 8 weeks in the treatment course. Two researchers performed and evaluated M-mode, B-mode, and four-dimensional (4D) echocardiography. Bland-Altman plots were created to show the bias and limits of agreement when comparing echocardiographic modalities. Simple linear regression and Pearson correlation were applied to evaluate interobserver variability. Six weeks after the first DOX injection, LVEF, radial LV fractional shortening, LV end-systolic volume, and LV end-diastolic volume were significantly reduced compared with baseline. LV dysfunction and dilation became more pronounced after 8 weeks of DOX treatment. For all parameters, 4D- and M-mode showed the lowest bias and narrowest limits of agreement. The correlation between the researchers' measurements was strong for most parameters. CONCLUSION: Our rat model of DOX-induced cardiotoxicity demonstrates that volumetric changes are more pronounced. Both 4D- and M-mode imaging techniques proved effective and reliable compared with the standard B-mode approach, with minimal interobserver variability, indicating strong reproducibility.