Insufficient production of erythropoietin (EPO) from the injured kidney is the major reason for anemia, while lack of EPO would further aggravate the kidney injury and make a “vicious cycle.” In this study, we dissected the change of endogenous EPO signaling in the injured kidney by spatial transcriptomic analysis and validated the dual beneficial effects of local recombinant EPO administration on both anemia correction and kidney protection. This evidence concerns the gene EPO and anemia.