Abstract: Objective: To investigate the effect and mechanism of Hippophae rhamnoides flavone (HRF) on polycystic ovarian syndrome (PCOS) in rats, and to provide new ideas for the prevention and treatment of PCOS. Methods: A PCOS rat model was duplicated by giving rats a high-fat diet combined with the intragastric administration of letrozole, and the model rats were randomly divided into model group, low-dose HRF group (200 mg/kg HRF), high-dose HRF group (400 mg/kg HRF) and metformin group (100 mg/kg). Changes in the related indicators were detected on the 21 d after the rats were administered with the different agents by gavage. Results: Compared with that in the model group, the ovarian index, the percentage of interestrus temporal image, the fasting blood glucose (FBG) level, the fasting insulin (FINS) content, the insulin resistance index (HOMA-IR), the activities of serum luteinizing hormone (LH) and testosterone (T), the levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and C reactive protein (CRP) of rats in low- and high-dose HRF groups were respectively decreased significantly (P<0.05, P<0.01), while the activity of follicle stimulating hormone (FSH) was significantly increased (P<0.01). The histopathological morphology of ovarian tissue of rats treated with the low and high doses of HRF was improved, and the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factors-κBp65 (NF-κBp65) mRNAs as well as TLR4, MyD88 and p-NF-κBp65 proteins were significantly decreased (P<0.05, P<0.01). Conclusion: HRF could improve the symptoms of PCOS, alleviate the insulin resistance, regulate the level of sex hormones and repair the pathological changes in the ovarian tissue of rats with PCOS, and its mechanism may be related to its inhibition on the inflammatory response mediated by the TLR4/NF-κB signaling pathway.