CP/CPPS is identified as a urinary andrological diseases that afflicts men due to various discomforts. It is urgent and meaningful to develop the novel and effective treatments as a result of the unclear etiology and dismal therapeutic effect of CP. Lycopene (LYC) exerts a crucial role in numerous chronic inflammatory diseases owing to its potent antioxidant capacity.This study aimed to observe the effect of lycopene on chronic prostatitis and to explore the underlying mechanisms.A chronic prostatitis model with complete Freund's adjuvant (CFA) was established in this study. Afterwards, intragastric LYC or corn oil was administered daily for 4 consecutive weeks. Finally, the cardiac blood and prostate tissue samples were collected from rats to carry out related evaluation and testing.It was found in this study that lycopene alleviated changes in prostate histopathology compared with those in the CFA-induced CP model rats without lycopene treatment. Furthermore, lycopene was suggested to reduce the levels of chemokines MCP1 and MIP-1α, down-regulate the expression levels of cytokines (such as TNFα, IL-1β, IL-2, and IL-6), and up-regulate those of CAT, GSH-PX and T-SOD,decrease that of MDA. Moreover, it also inhibited the phosphorylation of MAPKs, NFκB, and enhanced phosphorylation of the Nrf2 in the CP rat model.Findings in this study suggest that lycopene exerts potent anti-CP effects through alleviating inflammatory response and oxidative stress (OS), which is probably attributed to the interaction of NF-κB, MAPKs and Nrf2 signaling pathways in rats. As a natural antioxidant, lycopene may serve as a promising pharmaceutical preparation for treating chronic prostatitis.