Fibrosis is an outcome of irregular wound healing, manifesting as heightened scar formation marked by substantial extracellular matrix (ECM) accumulation, persistent inflammation, and gradual tissue or organ restructuring. This condition disrupts the normal tissue architecture, impairing organ function. Herein, the pivotal role of fibrosis in retinal repair mechanisms is compared in mice and zebrafish in responses to laser-induced injury. Our focus spans the intricate interplay between the gene regulation of ECM-involved protagonists and the dynamic development of fibrotic scars. We observed differential gene expression shifts and evaluated the effects of the fibrosis inhibitor pirfenidone (PFD) in the mouse model. These insights into retinal repair mechanisms contribute to a comprehensive understanding, guiding future therapeutic strategies for vision preservation.