Aim To observe the changes of plasma Urotensin-Ⅱ (UⅡ), Endothelial (ET) and Adrenomedullin (ADM) levels in chronic heart failure (CHF) and to investgate their clinical implications. Methods Plasma UⅡ, ET and ADM levels of 42 patients with CHF and 40 control subjects were measured by radioimmunoassay. In all the subjects, the left ventricular ejection fraction and the left ventricular mass index were measured by echocardiography. Results The plasma UⅡ levels were significantly lower in patients with CHF in comparison with that in control subjects (1.53±0.74 pmol/L vs 4.78±1.57 pmol/L, p<0.01). The plasma UⅡ levels after treatment were higher than before (3.63±1.09 pmol/L vs 1.53±0.74 pmol/L, p<0.01). A significant correlation of plasma UⅡ levels with the classes of cardiac function in CHF (r=-0.77,p<0.01), LVEF(r=0.80,p<0.01) and LVMI (r=-0.39, P=0.01) was observed. The plasma ET levels in patients were significantly higher than that in controls (51.83±11.38 ng/L vs 43.69±4.76 ng/L, p<0.05). The levels of plasma ET after treatment were higher than before (p>0.05). The plasma ADM levels in patients were significantly higher than that in controls (26.14±9.46 ng/L vs 19.10±4.74 ng/L, p<0.05). After therapeutic interventions, the plasma ADM levels were lower than before (p>0.05). Conclusions Vasoactive peptide might play a role in the pathophysiological process of CHF. UⅡ can evaluate left ventricular reconstitution and the severity of CHF. UⅡ may be of use in the diagnosis of heart failure. It may become a new target for the treatment of CHF.