In this study, we not only provide more evidence about the cardioprotective effect of raloxifene on TAC mice and we newly found that inflammation and IL-6/gp130/STAT3 signaling were activated in TAC murine heart but inhibited by raloxifene accompanied by the improvement of cardiac hypertrophy and heart failure, which is the mechanism of raloxifene differing from that of the others. The gene discussed is STAT3; the disease is heart failure.