Backgrounds and Purpose: Angiopoietin-1 (Ang 1) has potential therapeutic applications in inducing angiogenesis, enhancing endothelial cell survival and activation of Akt473 and MAPKp42/44 in cardiomyocyte. COMP-Angiopoietin 1 (COMP-Ang 1), a potent Ang 1 variant, is replaced the N-terminal portion of Ang 1 with short coiled-coil domain of cartilage oligomeric matrix protein (COMP). We hypothesized that COMP-Ang 1 attenuate ventricular remodeling, so-called ischemic protection, in a rat model of myocardial infarction (MI) by possible activation of survival pathway and/or angiogenesis. Methods: To evaluate the effect of COMP-Ang 1 for remodeling in a rat model of MI, the dose of 50��� of COMP-Ang 1 was injected at ischemic zone. MI was induced by 5-hours coronary ligation followed by reperfusion. Histologic analysis and functional improvement by echocardiography were evaluated at 2 weeks after MI. Expression of Akt and ERK were evaluated by Western blot for possible activation of survival pathway. Results: COMP-Ang 1 markedly attenuated wall thickness of infarction zone (control vs COMP-Ang 1, 0.71짹0.15 vs 10.14짹1.31 mm, p<0.05), ventricular dilation (1.03짹0.05 vs 0.94짹0.10 mm, p<0.05) and improved fractional shortening (14짹3.7 vs 20짹8.4 %, p<0.05). Vessel formation and vWF expression were increased at infarct and border-zone by Masson-trichome staining and immnunohistochemstry. At serial time points(0.5, 2, 4, 5.5, 7, 9, 24 hours) after injection of COMP-Ang 1 at ischemic region, COMP-Ang 1 remains until 5.5 hours (=30 minutes after reperfusion) by Western blotting using FLAG-antibody. Expression of total ERK and Akt levels was not changed. Expression of phospho-ERK was decreased at the all time points and phopho-Akt was increased at 7, 9, 24 hours in Westren blotting. Conclusions: COMP-Ang 1 markedly attenuates left ventricular remodeling in a rat model of MI. This findings suggest Comp-Ang 1 is an effective alternative to native Ang 1 for therapeutic angiogenesis in vivo.