Objective To investigate the role periurethral fibrosis secondary to chronic prostatic inflammation as a potential contributing factor to the etiology of lower urinary tract symptoms (LUTS) in male patients. Methods Periurethral prostate tissue from 30 consecutive patients who underwent retropubic radical prostatectomy for prostate cancer was analyzed. We circumferentially performed 16 periurethral core bench biopsies on each radical prostatectomy specimen to evaluate the extent of periurethral inflammatory infiltrate and collagen and elastin amount. The clinical and urodynamic findings and the collagen and elastin periurethral amount in patients with or without inflammation were compared using the Mann-Whitney U test and the Pearson χ2 test. Spearman correlation analysis tested the association between variables. Results Of the 30 patients, 21 (70%) presented with inflammatory infiltration and 9 (30%) had no inflammation. A significant difference was found between the 2 groups in International Prostate Symptom Score (IPSS; P  = .03) and in urodymanics findings by Schafer class ( P  = .01) and Abrams Griffiths number ( P  = .002). The histologic evaluation showed a higher collagen quantity ( P  = .04) and lower, albeit not statistically significant, elastin amount ( P  = .19) in the inflammation group. A positive association was observed between IPSS with inflammation grading ( r  = 0.507; P  = .004) and collagen content ( r  = 0.649; P  <.001), whereas IPSS was correlated negatively with elastin content ( r  = −0.565; P  = .001). Conclusion Prostate inflammation may induce fibrotic changes in periurethral prostatic tissues, and this may eventually promote urethral stiffness and LUTS. Patients experiencing prostate-related LUTS could benefit from anti-inflammatory therapies, used alone or combined with the currently prescribed regimen.