Transient receptor potential (TRP) family plays important roles in cardiovascular system. We investigated the relationship between transient receptor potential channel subfamily M6 (TRPM6) and atrial fibrosis in rheumatic heart disease patients with atrial fibrillation (AF).The right atrial tissue samples were obtained from 64 patients with rheumatic heart diseases who underwent heart valve replacement surgery, and composed of 34 sinus rhythm (SR) patients and 30 AF patients. Hematoxylin and Eosin (HE) staining was used to observe cross-sectional area (CSA) of myocardial cell. Masson staining and measurement of connective tissue growth factor (CTGF), transforming growth factor beta 1 (TGF-β 1), and collagen type I/III (Collagen I/III) were performed to determine atrial fibrosis. The mRNA and protein levels of TRPM6 were detected by real-time quantitative polymerase chain reaction (RT-PCR) and western blotting, respectively.Marked increases were observed in CSA of myocardial cell and myocardial collagen volume fraction in AF group compared with the SR group (all P<0.05). The mRNA levels of myocardial fibrosis markers (CTGF, TGF-beta 1, Collagen I/III) in AF group increased significantly compared to the SR group (all P<0.05). TRPM6 mRNA and protein levels in AF group were elevated markedly in comparison with SR group (P<0.01).These findings revealed that increased TRPM6 mRNA and protein levels may contribute to atrial fibrosis, and suggested that TRPM6 might be involved in AF development by promoting fibrogenesis.