Aim To explore the effect of liver X receptor-β(LXRβ) on chronic heart failure after myocardial infarction(MI) in mice. Methods The MI model was established by ligation of left anterior descending coronary artery in wild type(WT) mice and LXRβ gene knock-out(LXRβ－/－) mice. Third day after MI, cleaved caspase-3 was detected by Western blot, apoptosis of cardiac muscle cells was evaluated by terminal dUTP nick end labling(TUNEL) staining, and expressions of proinflammatory cytokines tumor necrosis factor α and interleukin-6 were detected by quantitative real-time polymerase chain reaction(qRT-PCR). Fourth week after MI, left ventricular function was assessed with ultrasonic echocardiography, myocardial infarct size was evaluated by triphenyl tetrazolium chloride(TTC) staining, myocardial fibrosis was observed by using Masson trichrome staining and α-smooth muscle actin(α-SMA) staining, and matrix metalloproteinase-9 and type Ⅰ collagen were detected by qRT-PCR to further assess myocardial fibrosis. Results Compared with WT mice, third day after MI, LXRβ－/－ mice exhibited more myocardial cell apoptosis and inflammation in the infarct area； Fourth week after MI, LXRβ－/－ mice showed a significant increase in infarct size, reduced ejection fraction and aggravated left ventricular dilation and enhanced myocardial fibrosis. Conclusions LXRβ gene knock-out aggravates the pathological damage and left ventricular remodeling after MI. As a targeted drug node, LXRβ may contribute to the treatment of MI.