Given that it remains unclear how cilostazol mitigates diabetes-associated vasculopathy through RAGE and its downstream signaling, the results of this study offer new insight into the signal transduction pathways that regulate cilostazol-mediated protection against HG-induced VSMC injury, and emphasize the involvement of RAGE signaling and downstream RAGE/ERK/NF-κB pathways. Here, AGER is linked to vascular disorder.