AIM: To observe the vascular remodeling of eriodictyol (EDT) in spontaneously hypertensive rats (SHRs) by inhibiting TLR4/NF-kB signaling and to investigate the potential mechanism of action. METHODS: WKY normal control, SHRs model and EDT administration (EDT 120 mg/kg, SHRs + EDT) group were set for 20 weeks. Tail cuff method for blood BP measurement (SBP, DBP and MBP). Ultrasonic detection of pulse wave velocity (PWV). The aortic media membrane thickness (MT) was visualized by HE staining. The percentage of aortic collagen (VFC) changes were observed by MASSON staining, Serum content of TNF-α, IL-6, and IL-10 was measured by ELISA. The TNF-α, IL-6, and IL-10 mRNA changes in the aorta were detected by q-PCR. The aortic Collagen I and Collagen Ⅲ expression was observed by immunohistochemistry, WB measured the expression of aortic TGF-β1, MMP-2, MMP-9, TLR4, p-IкBa, IкBa, p-p65 and p65. RESULTS: After 20 weeks of EDT administration, SBP, DBP, MBP and PWV of SHRs were significantly decreased, MT and VFC of aorta were significantly decreased, and protein expressions of Collagen Ⅰ, Collagen Ⅲ, TGF-β1, MMP-2, MMP-9, TLR4, p-I Camba and p-p65 were significantly decreased. CONCLUSION: After long-term administration of EDT could inhibit TLR4 / NF-κB signaling and exert anti-inflammatory effects, thus reducing TGF-β1, MMP-2 and MMP-9 expression, decreasing collagen content, and finally improving aortic remodeling and sclerosis of SHRs.