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Purpose: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, NIH category Ⅲ) accounts for 90-95% of prostatitis cases. However, standard treatment has not yet been established. It is known that polyphenols have an inhibitory effect on inflammation by their antioxidative capacity, and oligonol, a polyphenol derivative, has much higher bioavailability and bioactivity than common polyphenols. We investigated the anti-inflammatory effects and mechanisms of oligonol in estradiol-induced prostatitis rat models. Materials and Methods: Prostatitis was induced by 17 beta-estradiol (E2) and dihydrotestosterone (DHT) in Wistar male rats (n = 20). Ten rats were placed in the oligonol-treated group and 10 in the E2 + DHT-treated group. The other 10 rats were also included as normal control group. Oligonol (60 mg/kg/day) was administered via gavage tube for 4 weeks. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and tumor necrosis factor-alpha (TNF-α) were quantified, and phosphorylation of Ik Ba and histological changes were also evaluated in prostatic tissue. Results: The SOD and GPx activity showed tendencies to increase in the oligonol-treated group compared to the normal control group. TNF-α expression was slightly reduced in the oligonol-treated group. Western blotting demonstrated that phosphorylation of I kBa in the oligonol-treated group was significantly lower than in the normal control group. The E2 + DHT-treated group revealed severe atrophy of acinar epithelial cells and infiltration of leukocytes and lymphocytes in the prostate, however, the oligonol-treated group showed overall reduction in inflammatory features. Conclusion: This study demonstrates that oligonol improves estradiol-induced non-bacterial prostatitis by regulating phosphorylation of I kBa. These findings suggest that oligonol has a beneficial effect on prevention and treatment of CP/CPPS.