Objective: To investigate role of Wnt/β-catenin pathway on high glucose-induced H9c2 myocardial cell apoptosis, and evaluate the relationship between Wnt/β-catenin and autophagy. Methods: H9c2 myocardial cell apoptosis model induced by high glucose was constructed, cell viability and apoptosis ratio was determined by CCK-8 and flow cytometry, Western blot analysis was used to detect the expression of caspase-3, LC3-Ⅱ/LC3-Ⅰ, Axin-1 and β-catenin in H9c2 myocardial cell. Results: Cell viability fell sharply, and protein expression of caspase-3 were remarkably increased in H9c2 myocardial cell treatment with 50 mmol/L high glucose for 48 h compared with control cells. Furthermore, Western blot analysis revealed that high glucose triggered Wnt pathways, thus suppressed the expression level of Axin-1 and promoted β-catenin expression and LC3-Ⅱ/LC3-Ⅰ ratio. Pretreatment by dickkopf-1(DKK-1) attenuated HG-induced apoptosis of H9c2 myocardial cell, down-regulated the activity of Axin-1, and significantly increased the expression of β-catenin and LC3-Ⅱ/LC3-Ⅰ ratio, and reduced the production of β-catenin. Conclusion: This study has demonstrated that Wnt/β-catenin pathway was activated on HG-induced injury and apoptosis in H9c2 cells and that was associated with inhibition of autophagy pathways. Furthermore, blocking the Wnt/β-catenin signaling with the selective antagonist DKK-1 resulted in enhancement of autophagy, and inhibition of the apoptotic index in high glucose-induced H9c2 myocardial cell.