The spread of COVID-19 has greatly threatened human health and economic growth. Angiotensin-converting enzyme 2 (ACE2) is a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). By attaching to ACE2, SARS-COV-2 reduces its expression and induces lung injury. Vitamin D can inhibit the progression of COVID-19 by inhibiting the activity of ROCK pathway, up-regulating ACE2 expression and bioavailability, and slowing down the adverse reactions caused by AngⅡ accumulation. This study explored a novel mechanism, i.e., vitamin D protects against COVID-19-induced injury by upregulating ACE2 expression. It provides theoretical guidance for the role of Vitamin D in the prevention and treatment of COVID-19.