Abstract Context: Cyclosorus acuminatus (Houtt.) Nakai (Thelypteridaceae) is used in Chinese traditional medicine for inflammation and pyretic stranguria. Objective: This study investigates the prostatic protective potential of the flavonoid-rich [(2S)-5,7,5'-trihydroxyflavanone glycosides] fraction from C. acuminatus (FCA). Materials and methods: Chronic non-bacterial prostatitis (CNBP) was induced by injecting 20 μl of 1% carrageenan into the rat prostate. Subsequently, FCA (150 or 300 mg/kg/d) was orally given once a day for 4 weeks. Finally, the levels of proinflammatory cytokines and the prostatic expression of peroxisome proliferator activated receptor-γ (PPAR-γ) were evaluated. Results: Treatment with 300 mg/kg/d FCA ameliorated the carrageenan-induced higher prostatic index (PI) state and proinflammatory cytokines levels (NFκB from 2602 ± 588 to 1348 ± 300 pg/ml, TNF-α from 151.6 ± 10.4 to 126.0 ± 3.52 pg/ml, IL-1β from 153.7 ± 14.8 to 63.9 ± 6.7 pg/ml, COX-2 from 313.3 ± 16.5 to 263.1 ± 15.1 pg/ml, PGE from 1532 ± 130 to 864 ± 126 pg/ml, NOS from 33.7 ± 3.0 to 23.6 ± 1.6 U/mg protein, and NO from 40.3 ± 2.9 to 27.1 ± 2.9 μmol/g protein) as well as regulated the prostatic expression of PPAR-γ (increased about 3.50-fold) when compared to the rat model of prostatitis. Discussion and conclusion: FCA could exert a prostatic protective response via modulating the prostatic expression of PPAR-γ and eventually alleviating the NFκB dependent inflammatory response.