While the bone morphogenetic protein-7 (BMP-7) is a well-known therapeutic growth factor reverting many fibrotic diseases, including peritoneal fibrosis by peritoneal dialysis (PD), soluble growth factors are largely limited in clinical applications owing to their short half-life in clinical settings . Recently, we developed a novel drug delivery model using protein transduction domains (PTD) overcoming limitation of soluble recombinant proteins, including bone morphogenetic protein-7 (BMP-7). This study aims at evaluating the therapeutic effects of PTD-BMP-7 consisted of PTD and full-length BMP-7 on epithelial-mesenchymal transition (EMT) -related fibrosis . Human peritoneal mesothelial cells (HPMCs) were then treated with TGF-ß1 or TGF-ß1 + PTD-BMP-7 . Peritoneal dialysis (PD) catheters were inserted into Sprague-Dawley rats, and these rats were infused intra-peritoneally with saline, peritoneal dialysis fluid (PDF) or PDF + PTD-BMP-7 . In vitro, TGF-ß1 treatment significantly increased fibronectin, type I collagen, α-SMA and Snail expression, while reducing E-cadherin expression in HPMCs (P <.001). PTD-BMP-7 treatment ameliorated TGF-ß1-induced fibronectin, type I collagen, α-SMA and Snail expression, and restored E-cadherin expression in HPMCs (P <.001). In vivo, the expressions of EMT-related molecules and the thickness of the sub-mesothelial layer were significantly increased in the peritoneum of rats treated with PDF, and these changes were significantly abrogated by the intra-peritoneal administration of PTD-BMP-7 . PTD-BMP-7 treatment significantly inhibited the progression of established PD fibrosis . These findings suggest that PTD-BMP-7, as a prodrug of BMP-7, can be an effective therapeutic agent for peritoneal fibrosis in PD patients.