The present study yielded the following novel findings: (1) G1 treatment reduced blood glucose and ameliorated the diabetes-induced loss in body weight and NO serum levels in the diabetic OVX rats; (2) Administration of G1 for 8 wk could partially prevent the functional changes on vascular reactivity in the diabetic OVX rats; (3) The dose-dependent vasoconstrictor responses to PE are significantly attenuated following the acute G1 administration in the diabetic OVX rats; and (4) The activation of GPR30 induced the phosphorylation of eNOS, which enhanced the NO-dependent vasodilation. The gene discussed is GPER1; the disease is diabetes mellitus.