Background: Chronic non-bacterial prostatitis (CNP) is a widespread disease of the male reproductive system. MiR-181c can be expressed in prostate tissue, but it has not been reported in CNP. This study aims to investigate the role of miR-181c in CNP and its mechanism of action on CNP, providing new ideas for the treatment and diagnosis of CNP. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were applied to determine miR-181c expression in clinical CP patients, CNP rats, and LPS-induced human prostaglandin epithelial cell RWPE-1. Then, luciferase reporter assay was performed to verify the targeting relation between miR-181c and COX-2. Through cell transfection experiments, the effect of mi-181c on the expression of COX2 and PGE2 was studied, and the effect of miR-181c/COX-2 on the proliferation of prostate epithelial cells was also explored. Results: qRT-PCR and Western blotting analysis revealed that miR-181c was low expressed in prostate tissue of CP patients and CNP rats and human prostaglandin epithelial cell RWPE-1. The luciferase reporter assay confirmed the targeting relation between miR-181c and COX-2. And miR-181c overexpression reduced the expression of COX-2 and PGE2 and suppressed the proliferation of prostate epithelial cells. COX-2 up-regulation reversed these effects caused by overexpression of miR-181c. Conclusions: miR-181c inhibited the proliferation of prostate epithelial cells through negatively regulating COX-2 to alleviate chronic non-bacterial prostatitis. Keywords: Chronic non-bacterial prostatitis, miR-181c, COX-2, prostatic epithelial cell, proliferation