Esculetin, also known as 6,7-dihydroxycoumarin, is a coumarin-derived phytochemical that has shown effects against ischemic stroke. Additionally, chemokine-like factor 1 (CKLF1) has been revealed in previous findings to be a target for stroke when using coumarin-derived compounds. The effects of esculetin and the potential involvement of CKLF1 were tested in photothrombotic stroke in mice.