Benign prostatic hyperplasia (BPH) is a common disrupting health problem affects elderly men. However, different mechanisms underlying the pathogenesis of BPH are still unclear. For the first time, we tried to explore the role of interleukin 1β (IL1β) antagonist, diacerein (DIA) in BPH and different pathways involved in mediating such effect. BPH was induced using testosterone propionate (TP) (5 mg/kg/day) for 4 weeks subcutaneous injection followed by DIA (50 mg/kg/day) orally for 4 weeks. We evaluated the histopathological changes, prostate weight, dihydrotestosterone (DHT), prostate specific antigen (PSA), and total antioxidant capacity (TAC) in serum. Moreover, malondialdehyde (MDA), heme oxygenase 1 (HO1), nuclear factor erythroid 2–related factor 2 (Nrf2), caspase3, IL1β expressions, and proliferating cell nuclear antigen (PCNA) were measured in tissue specimens. Our results confirmed the induction of BPH by histopathological examination which revealed typical changes of BPH with dysplastic features. Moreover, there are significant increases in prostate weights, DHT, PSA, PCNA, MDA, and IL1β but significant decreases in TAC, HO1, Nrf2 and caspase 3. Interestingly, DIA significantly improved BPH induced histopathological and biochemical changes that is not differing from control group without dysplastic changes. This is mostly attributed to blocking of IL1β, anti-oxidant, apoptotic properties with activation of Nrf2/HO1 pathway.