Aim: To study whether urotensin Ⅱ (UⅡ), a potent vasoconstrictive peptide, is involved in the development of cardiac hypertrophy and fibrogenesis of rats induced by isoproterenol (ISO). Methods: Thirty male Wistar rats were randomly divided into 3 groups. Group 1 was the healthy control group, group 2 was the ISO group, and group 3 was the ISO+UⅡ group. In groups 2 and 3, ISO (5 mg-kg-1.d-1) was given (sc) once daily for 7 d. Group 3 was also given UⅡ in the first day [3 nmol/kg (5 μg/kg), iv], followed by sc (1.5 μg/kg) twice daily. Group 1 received 0.9% saline. UⅡ receptor (UT) mRNA expression was determined by RT-PCR. The contents of UⅡ and angiotensin Ⅱ (Ang Ⅱ) were determined by radioimmunoassay. In vitro, the effects of UⅡ on DNA/collagen synthesis of cardiac fibroblasts were deter-mined by [3H]thymidine/[3H]proline incorporation. Results: The ratio of heart weight/body weight, plasma lactate dehydrogenase activity, myocardial malondialdehyde and hydroxyproline concentration increased significantly in the ISO group, as well as UT mRNA expression, plasma and cardiac UⅡ and ventricu-lar Ang Ⅱ, compared with the control group (P<0.01). ISO induced significant myocardial fibrogenesis. Moreover, UⅡ+ISO co-treatment significantly increased the changes of biochemical markers of injury and the degree of cardiac hypertro-phy and fibrosis. In vitro, 5x10-9-5x 10-7 mol/L UⅡ stimulated [3]thymidine/[3H] proline incorporation into cardiac fibroblasts in a dose-dependent manner (P<0.01).Conclusion: These results suggest that UⅡ was involved in the development of cardiac fibrosis and hypertrophy by synergistic effects with ISO.