The mechanistic link between chronic inflammation and prostate cancer (PCa) is missing, despite accumulating evidence suggests a role for inflammation in the etiology of this disease. We hypothesized that nuclear factor-kappaB (NF-κβ) activation might result in the production of signals for mononuclear cell (MNC) accumulation into the prostate. We used transgenic NF-κB-Luc Tag mice that demonstrate the highest levels of NF-κB-dependent luminescence in vivo and ex vivo at 4 h after i/v IL-1β administration. In these mice, IL-1β-induced NF-κB activation correlated with MNC trafficking, expression of chemokines and IL-17 in the prostate. Next we determined the possibility of IL-17 producing cells to be targets of specific pro-inflammatory signals that initiate inflammation at sites of prostate inflammatory atrophy (PIA) in PCa patients. To immunophenotype the inflammatory cell infiltrates in formalin-fixed paraffin-embedded whole mount radical prostatectomy specimens two-color staining was employed. MNC were the predominant IL-17 producing cells in PIA lesions. The number of IL-17 positive cells in the acini of PIA lesions was 5-fold higher than in PCa areas; and 3-fold higher than around PCa or other pathologic patterns studied. Taken together, our findings support the hypothesis that NF-κB provides a mechanistic link between cell-mediated inflammation, PCa development and its subsequent progression.