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Activin receptor-like kinase 7 (ALK7) is associated with lipometabolism and insulin sensitivity.Our pervious study demonstrated that ALK7 participated in high glucose-induced cardiomyocytes apoptosis.The aim of our study was to investigate whether ALK7 plays an important role in modulating diabetic cardiomyopathy (DCM) and the mechanisms involved.The model of diabetes was induced in male Sprague-Dawley rats (120-140g) by high-fat diet and intraperitoneal injections of low-dose streptozotocin (30 mg/kg).Animals were separated into 4 groups: control, DM, DM with ALK7 silencing, and DM with vehicle control.The cardiac function was assessed by catheterization.Histopathologic analyses of collagen content and apoptosis rate, and protein analyses of ALK7, Srnad2/3, Akt, Caspase3 and Bax/Bcl2 were performed.The results showed a rat model of type 2 DCM with hyperglycemia, severe insulin resistance, left ventricular dysfunction and structural remodeling.With ALK7 silencing, the apoptotic cell death (apoptosis rate assessed by TUNEL, ratio of Bax/Bcl2 and expression of cleaved Caspase3), fibrosis areas, and collagen Ⅰ-to-Ⅲ ratio decreased significantly.The insulin resistance and diastolic dysfunction were also ameliorated by ALK7 silencing.Furthermore, the depressed phosphorylation of Akt restored while elevated phosphorylation of Smad2/3 decreased after the silencing of ALK7.The results suggest ALK7 silencing plays a protective role in DCM and may serve as a potential target for the treatment of human DCM.