Objective To study the mechanism of Jiedu Huoxue Decoction(JDHXD) in treating type III prostatitis through ERK/p38 MAPK signaling pathway. Methods The rat model of chronic prostatitis was established by testectomy and using estradiol benzoate(EB). Thirty-six SD rats were randomly divided into sham(normal saline, 4 mL·kg-1), model(normal saline, 4 mL·kg-1), positive drug control (Qianliekang tablet suspension, 4 mL·kg-1), and JDHXD low(4mL·kg-1), medium(8mL·kg-1) and high dose(12mL·kg-1) groups, with 6 rats in each group. All animals were administered continuously for 30 days. The histopathological changes of rats in each group were observed by hematoxylin-eosin(HE) staining. The expression levels of related inflammatory factors and proteins were detected by immunohistochemistry, RT-PCR and Western Blot. Results Compared to the sham group, rats in model group had chronic prostatitis with an increase in hyperplasia, edema, and inflammatory infiltration. However, JDHXD at different doses resulted in a reduction or disappearance of hyperplasia, edema, and inflammatory infiltration. The results of immunohistochemistry showed that the expression of p38, P-p38, STAT3 and P-STAT3 was elevated in the model group, but decreased in the positive drug control group and JDHXD groups. RT-PCR results showed that Qianliekang Tablets and JDHXD down-regulated the expression levels of TNF-α, IL-2, IL-6 and other cytokines in prostate tissue of rats at mRNA level. The results of Western Blot showed that p38, P-p38, P-ERK1/2, STAT3 and P-STAT3 were highly expressed in the process of disease progression in rats, while JDHXD down-regulated their expression, thereby inhibiting the excessive activation of related inflammatory factors. Conclusion JDHXD inhibits the excessive activation of ERK/p38 MAPK signaling pathway, thereby down-regulating the expression of IL-2, IL-6, TNF-α and other inflammatory factors, to improve the prostate tissue inflammatory infiltration and improve the inflammatory reaction.