This study is to explore the effects of two Suppressors of Cytokine Signalling (SOCS) members, namely SOCS-1 and -3, on the regulation of cardiomyocyte hypertrophic response induced by Angiotensin-2 (AngII). Rat neonatal cardiomyocytes culture were cultured and treated with Angiotensin II. After SOCS1 and SOCS3 inhibition by si-RNA transfection, the cellular hypertrophic response indicated by cell size and protein contain per cell were determined. AngII stimulation dramatically increased the cellular size, protein content and the SOCS-1 and -3 mRNA expression levels in a dose dependent manner. The SOCS3 protein levels were augmented by AngII treatment while the SOCS1 remain unchanged. SOCS3 si-RNA induced a 75% reduction in SOCS3 protein expression without changing SOCS1 protein. With SOCS3 si-RNA transfection, cells showed a dramatically reduction in cell surface and protein content, while the inhibition of SOCS1 did not change the cellular hypertrophy after AngII treatment. These data suggest that SOCS3 involved in Ang II induced cardiomyocyte hypertrophic response.