ABSTRACT Soft tissue defects caused by adipose tissue loss can result in various conditions such as lipodystrophy in congenital diseases, trauma secondary to ageing, and mastectomy in breast cancer; fat grafting is commonly performed to restore these defects. Although various enrichment strategies have been studied, novel therapeutics that are cost-effective, safe, technologically easy to manufacture, and minimally invasive are required. In this study, we identified a novel peptide derived from plasminogen, named plasminogen-derived peptide-1 (PLP-1), which showed adipogenic differentiation potential and led to an increase in the expression levels of adiponectin, C1Q and collagen domain containing protein, fatty acid-binding protein 4, and CCAAT/enhancer-binding protein-alpha. In vivo experiments confirmed an increase in the rate of adipocyte differentiation and the expression levels of CD31 in the PLP-1-treated mice groups. These results suggested that PLP-1 plays an important role in promoting the differentiation of preadipocytes and may be useful for developing therapeutic approaches to treat adipose tissue defects.