Background and Purpose: One of the most bothersome disorders affecting elderly men is benign prostatic hyperplasia (BPH). Prostatic inflammation is the driving force behind hyperplasia. A pro-inflammatory response in the prostate has been linked to a number of cytokines and growth factors. The current study evaluated the association between inflammation and hyperplasia in BPH. Experimental Approach: A standard selective COX-2 inhibitor; Celecoxib (CXB) (10 and 20 mg/kg) was injected i.p. daily into male Wister rats for three weeks. From the second week, testosterone (TST) (3 mg/kg) was injected s.c. daily to induce BPH. Key Results: In TST-treated rats, there was a marked increase in COX-2, concurrently with an elevation in prostate weight and index as well. Moreover, TST-induced COX-2 was elucidated by the deleterious changes in histopathological cytoskeleton. In addition, overexpression of PGE2 , NF-κB (p65) , and IL-6 could be attributed to COX-2 induced by TST. Additionally, COX-2-derived PGE2 increased the activity of ADAM-17 , TGF-α , and TNF-α . Consequently, EGFR –ERK1/2 pathway was activated. Collectively, the normal balance between prostatic cell proliferation (Bcl-2 and Cyclin D1) and apoptosis (Bax ) was disrupted. By using CXB, the effects of TST-induced COX-2 were reversed. Conclusion and Implications: It can be concluded that COX-2 is critical for overactivation of EGFR–ERK1/2 pathway in TST-induced BPH. Concisely, COX-2 induces ERK1/2 pathway via PGE2–ADAM-17 catalyzed shedding of TGF-α in TST-induced BPH. In addition, the present work augments the functional correlation between inflammation and hyperplasia in BPH.