Purpose : Myocardial strain analysis has been reported useful in early detection of left ventricular systolic dysfunction (LVD) in doxorubicin-treated animal model. However, the administration protocol of doxorubicin to induce LVD in rats was not standardized between studies. This study was designed to determine the effective and applicable protocol of doxorubicin administration for animal heart failure model by comparing two different administration protocols. Methods and results: Twenty nine male rats (343.3짹35.0g) were assigned in three groups; low dose frequent administration of doxorubicin (Group I; n=10), high dose weekly administration (Group II; n=11) and control group (Group III; n=9). In group I, doxorubicin was administered intraperitoneally, 1.25mg/kg, every other day; in group II, doxorubicin of 5mg/kg, once in a week; in group III, saline of 1.25ml/kg, every other day. Total amount of administered doxorubicin was 20mg/kg in both group I and II. Echocardiography was taken at baseline, first, second and fourth week and left ventricular volume, ejection fraction (LVEF) were obtained. Strain (S) and strain rate (SR) of mid-posterior wall were acquired from LV short axis view by color coded tissue velocity images. At baseline, there was no difference in body weight or echocardiographic parameters between groups. At second week, group I and II showed decrease in S (70.0 vs 53.2%, p=0.004, 72.0 vs 56.7 %, p=0.031) but SR decreased in group I only (16.5 vs 13.2 cm/s, p=0.019; 15.7 vs 14.0 cm/s, p=0.217). There was no decrease in LVEF in both groups at second week. At fourth week, in both group I and II, SR, S and LVEF decreased compared to baseline. (group I; 16.5 vs 11.9 cm/s, p=0.004, 70.0 vs 62.4%, p=0.019, 81.0 vs 71.3 %, p<0.01, Group II; 15.7 vs 10.5 cm/s, p=0.007, 72.0 vs 53.1 %, p=0.030, 81.0 vs 68.2 %, p<0.01, respectively). In group III, there was no change in strain rate, strain and LVEF. At sixth week, only five rats survived in group II, while all rats were alive in group I and III. Conclusions : Both low dose frequent and high dose weekly protocols were effective in inducing LVD in rats, and the impairment of myocardial strain preceded the decrease in LVEF in both protocols. Strain rate decreased in group I earlier than in group II, which can be due to slower progression of LVD in group I. Deterioration of strain, strain rate and LVEF were more severe and mortality rate was higher in group II. Appropriate protocol of doxorubicin administration should be determined based on the objectives of individual researches and low dose frequent protocol is more suitable for the researches in chronic heart failure.