Background: Formation of the epicardium requires several cellular processes including migration, transformation, invasion, and differentiation in order to give rise to fibroblast, smooth muscle, coronary endothelial and myocyte cell lineages within the developing myocardium. Snai1 is a zinc finger transcription factor that plays an important role in regulating cell survival and fate during embryonic development and under pathological conditions. However, its role in avian epicardial development has not been examined. Results: Here we show that Snai1 is highly expressed in epicardial cells from as early as the proepicardial cell stage and its expression is maintained as proepicardial cells migrate and spread over the surface of the myocardium and undergo epicardial-to-mesenchymal transformation in the generation of epicardial-derived cells. Using multiple in vitro assays, we show that Snai1 overexpression in chick explants enhances proepicardial cell migration at Hamburger Hamilton Stage (HH St.) 16, and epicardial-to-mesenchymal transformation, cell migration, and invasion at HH St. 24. Further, we demonstrate that Snai1-mediated cell migration requires matrix metalloproteinase activity, and MMP15 is sufficient for this process. Conclusions: Together our data provide new insights into the multiple roles that Snai1 has in regulating avian epicardial development. Developmental Dynamics 242:699–708, 2013. © 2013 Wiley Periodicals, Inc.