Collective cell migration is critical for various physiological and pathological processes. In vitro wound healing assay has been widely used to study collective cell migration due to its technical simplicity and ability of revealing the complexity of collective cell migration. This project studies the function and importance of leader cells, the cells pulling cell monolayer migrating into free space, in endothelium and skin epithelial regeneration via plasma lithography enhanced in vitro wound healing assay. Despite leader cells have been identified in in vitro wound healing assays, little is known about their regulation and function on collective cell migration. First, I investigated the role of leader cells in endothelial cell collective migration. I found that the leader cell density is positively related with the cell monolayer migration rates. Second, we used this knowledge to study the effects of arsenic treatment on skin regeneration via in vitro wound healing assay. We found that low concentration of arsenic treatment can accelerate the keratinocyte monolayer migration. We further found that arsenic affected cell migration by modulating leader cell density through Nrf2 signaling pathway. As a conclusion of these studies, we evaluated the function of leader cells in collective cell migration, and elucidated the mechanism of arsenic treatment on skin regeneration.