Background Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common disease of urology, of which the pathogenesis and therapy remain to be further elucidated. Quercetin has been reported to improve the symptoms of CP/CPPS patients. We aimed to verify the therapeutic effect of quercetin on CP/CPPS and identify the mechanism responsible for it. Methods A novel CP/CPPS model induced with Complete Freund Adjuvant in Sprague Dawley rats was established and the prostates and blood specimens were harvested for further measurement after oral administration of quercetin for 4 weeks. Results Increased prostate index and infiltration of lymphocytes, up‐regulated expression of IL‐1β, IL‐2, IL‐6, IL‐17A, MCP1, and TNFα, decreased T‐SOD, CAT, GSH‐PX, and increased MDA, enhanced phosphorylation of NF‐κB, P38, ERK1/2, and SAPK/JNK were detected in CP/CPPS rat model. Quercetin was identified to ameliorate the histo‐pathologic changes, decrease the expression of pro‐inflammatory cytokines IL‐1β, IL‐2, IL‐6, IL‐17A, MCP1, and TNFα, improve anti‐oxidant capacity, and suppress the phosphorylation of NF‐κB and MAPKs. Conclusions Quercetin has specific protective effect on CP/CPPS, which is mediated by anti‐inflammation, anti‐oxidation, and at least partly through NF‐κB and MAPK signaling pathways.