Abstract： Objective： To explore the mechanism of quercetin in myocardial fibrosis in spontaneously hypertensive rats (SHR). Methods： Fifty SHRs were randomly divided into SHR group， Captopril group， low-，medium-，and high-dose of quercetin groups，with 10 in each group. Ten Wky rats were included in the Wky group. Captopril group was given Captopril 30 mg/kg by gavage，quercetin low-，medium-， and high-dose groups were given quercetin 20，50，and 100 mg/kg by gavage，respectively. Wky group and SHR groups were given equal amounts of 0.9% sodium chloride solution once a day for 12 consecutive weeks. The systolic blood pressure (SBP) of the rat tail artery was measured every 2 weeks using the tail cuff method.After administration， weigh the heart mass， and the rats were killed. Measure their left ventricular mass (LVM)， and calculate the left ventricular mass index (LVMI)， serum superoxide dismutase (SOD)， total antioxidant capacity (T-AOC) activity， and malondialdehyde (MDA) content were measured by colorimetry. mRNA and protein expressions of glycogen synthase kinase 3β(GSK-3β) in left ventricular tissue and non- receptor tyrosine kinase Fyn， nuclear factor E2- related factor 2 (Nrf2)， and protein expressions of collagen type Ⅰand Ⅲ (Collagen-Ⅰ and Collagen-Ⅲ) were detected by real- time fluorescence quantification- polymerase chain neaction (RT- PCR) and Western blot. Results： Compared with Wky group， SBP， heart mass， and LVMI in SHR group were significantly increased (P＜0.01). The activities of SOD and T- AOC in serum were significantly decreased， while the content of MDA was significantly increased (P＜0.01). The expressions of Collagen- Ⅰ and Collagen- Ⅲ in left ventricle were significantly increased (P＜0.01). The mRNA and protein expressions of Nrf2 and GSK-3β were significantly decreased (P＜0.01)， while the mRNA and protein expressions of Fyn were significantly increased (P＜ 0.01). Compared with SHR group， the SBP， heart mass， LVM， and LVMI of rats in Captopril group， quercetin low-，medium-，and high-dose groups were significantly decreased (P＜0.01). The activities of SOD and T- AOC in serum were significantly increased， while the content of MDA was significantly decreased (P＜0.05，P＜0.01). The protein expressions of Collagen-Ⅰ and Collagen-Ⅲ in the left ventricle of the medium- and high- dose quercetin groups were significantlys decreased (P＜0.01). The mRNA and protein expressions of Nrf2，GSK-3β in left ventricle of quercetin low-，medium-，and high-dose groups were significantly increased，while the mRNA and protein expressions of Fyn were significantly decreased (P＜0.05，P＜0.01). Conclusion：Quercetin can inhibit myocardial fibrosis in SHR，and its mechanism may be through down-regulating GSK- 3β/Fyn signaling pathway，activates Nrf2-induced antioxidant pathway and reduces oxidative stress response in SHR myocardial tissue.