These improvements were antagonized by estrogen-receptor antagonists, demonstrating that acacetin is dependent on estrogen-like action to reduce inflammatory cytokines, inhibit ERK pathway, down-regulate ARG2 expression, increase the expression of NO, vasodilate, improve aortic endothelial dysfunction and improve aortic fibrosis in SHR rats with insulin-resistant. This evidence concerns the gene ESR1 and Insulin resistance.