Background Tenascin-x, an extracellular matrix glycoprotein exclusively expressed in fibroblasts, can mediate fibrosis in the presence of collagen. Therefore, we have investigated its potential role in facilitating myocardial fibrosis and cardiac remodeling via the transforming growth factor-lβ1 and peroxisome proliferator-activated receptor γ(TGFβ1-PPARγ) pathway in alcoholic cardiomyopathy (ACM).Methods Experimental animals were divided into control (group A) and tenascin-x knock-out groups (group B)receiving alcohol. Six months post treatment, cardiac ejections fraction (EF), fractional shortening (FS), left ventricle end-diastole internal diameter (LVEDd) and collagen column fraction (CVF) were observed. Tenascin-x, smad-3, TGFβ1,smad-7 and PPARγ protein expression levels were detected by Western blotting.Results Six months post treatment, EF and FS values were higher in group B than in group A (P ＜0.05 and P ＜0.01,respectively), while LVEDd and CVF were lower in group B (P ＜0.05 and P ＜0.01, respectively). Tenascin-x, smad-3 and TGFβ1 protein expression levels were higher in group A, while smad-7 and PPARY levels were lower than in group B (P＜0.01), as measured by immunohistochemistry and Western blotting. Tenascin-x protein expression was negatively correlated with EF, FS, smad-7 and PPARγ, and positively correlated with LVEDd, CVF, smad-3, and TGFβ1 (P ＜0.001).Conclusion Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGFβ1 and downregulation of PPARγ.