Abstract: Objective To investigate the effect of Wnt-C59,a Wnt/β-catenin pathway inhibitor,on pathological cardiac hypertrophy and its mechanism. Methods 1In the in vivo study,male C57B/L mice（8-10 weeks of age,weight 18-22g）were performed with transverse aorta constriction（TAC）to induce pathological cardiac hypertrophy. The mice were randomly divided into sham group,Wnt-C59 group,TAC group and TAC+Wnt-C59 group.2In the in vitro study,0.1μmol/L angiotensin Ⅱ（Ang Ⅱ）was administered to neonatal rat ventricular myocytes（NRVM）for the emergence of pathological cardiac hypertrophy. NRVM were randomly divided into control group,control+ Wnt-C59 group,Ang Ⅱ group and Ang Ⅱ + Wnt-C59 group. Heart mass/body mass（HM/BM）,cardiac function and cross-sectional area（CSF）of cardiomyocytes were observed in the in vivo study.The surface area of NRVM,β-catenin nuclear translocation and the mRNA expressions of hypertrophy-related genes C-myc and Cyclin-D1 were evaluated in the in vitro study. Results Compared with TAC group,Wnt-C59 significantly reduced the increase of HM/BM TAC+Wnt-C59:（6.02±0.48）vs TAC:（7.45±1.15）mg/g,P＜0.05and CSF of myocytes induced by TAC,and improved cardiac functionEF:TAC+Wnt-C59:（59.29±4.61）% vs TAC:（48.60±2.72）%,P＜0.05. Compared with Ang Ⅱ group,Wnt-c59 significantly decreasedβ-catenin nuclear translocationAngⅡ+Wnt-C59:（15.90±4.11）% vs Ang Ⅱ:（25.27±6.69）%,P＜0.05and mRNA expressions of C-myc and Cyclin-D1. Conclusion Wnt-C59 exerts therapeutic effect on pathological cardiac hypertrophy,and its mechanism may be related to the inhibition ofβ-catenin nuclear translocation and transcription of its downstream hypertrophy genes,C-myc and Cyclin-D1.