In this study, we confirmed that canagliflozin significantly improved diabetes-induced cardiorenal dysfunction, and we also provided first evidence that diabetic or high glucose-induced CX3CL1 expression was inhibited markedly by canagliflozin in a glucose-lowering independent manner, suggesting that CX3CL1 is a potential target of SGLT2i. Here, CX3CL1 is linked to diabetes mellitus.