Endothelial dysfunction is a key factor in development of diabetic vascular complications. We and others reported that vegetable polyphenol morin (MO) and quercetin (QC) induced vascular endothelial relaxations through the Akt/eNOS signaling pathway. However, the relaxation pathway was fully unknown. In this study, we examined about the upstream of the Akt/eNOS signaling in diabetes. In aortas isolated from diabetic (DM) or control mice, MO and QC induced dose-dependent relaxation responses. Especially, DM aortas showed enhanced MO-induced relaxation responses relative to controls. The relaxation responses with MO were not significant in the presence of each PI3K inhibitor and AMPK inhibitor. Meanwhile, the relaxation responses with QC were attenuated in the presence of PI3K inhibitor. In the presence of AMPK inhibitor, the relaxation responses with QC were attenuated in DM but there were not significant in control. In this study, we showed that QC induced NO-dependent relaxation responses via PI3K/Akt/eNOS signaling pathway in control, notably AMPK/Akt/eNOS signaling in DM. Thus, it was suggested the possibility that MO and QC have different mechanism in relaxation, and that MO had the beneficial effect on the diabetes induced endothelial dysfunction.