Aim To explore the role of cardiac-specific overexpression of RIP140 in cardiac function and inflammation signaling pathway.Methods Direct intra-myocardial injection of adenovirus vector expressing RIP140 drove transgene expression in heart tissue.RIP140 overexpression was confirmed using immunofluorescence technique in heart.Cardiac function was assessed by echocardiographic and hemodynamic assessment.TNF-α,IL-2 and IL-1β inflammatory cytokines were detected by ELISA,and the protein levels of p65 and IκB-α were measured by Western blot.Results Adenovirus-mediated foreign gene of RIP140 was successfully transferred in cardiac tissue.RIP140 overexpression in heart induced ventricular dilation,decreased left ventricular ejection fraction and cardiac malfunction,as well as increased releases of TNF-α,IL-2 and IL-1β inflammatory cytokines,p65 protein translocation into the nucleus and IκB-α protein degradation in cytoplasm.Conclusion Adenovirus-mediated RIP140 overexpression in cardiac tissue impairs cardiac function,activates NF-κB/p65 inflammatory signaling pathway and induces the release of inflammatory cytokines.