Background and objective: Benign prostatic hyperplasia (BPH) is a typical nonmalignant growth of the prostate in the elderly. Crocin, a bioactive component of Crocus sativus L., commonly known as saffron, is known to have an anti-proliferative activity against numerous types of cancer, including prostate cancer. This study investigated the effects of crocin on testosterone-induced BPH development in rats. Materials and methods: The study sample included three groups of adult male rats (3 months old, weighed 250 g): the control group received corn oil only, the second and the third groups were injected with testosterone (3 mg/kg dissolved in corn oil) subcutaneously. The second group was considered as testosterone-induced BPH (untreated) while the third groups were assigned as testosterone-induced BPH-crocin treated group (100 mg/kg orally for 14 days). Results: After animal sacrifice, histopathological analysis of the prostate tissues was performed in parallel with gene expression of proliferation (PCNA), inflammation (IL-6), and vascularization (VEGF-A) markers, analyzed by qRT-PCR. Crocin treatment significantly reduced prostate index and the thickness of the epithelial layer in rats with BPH. Additionally, the mRNA expression levels of PCNA, a marker of cell proliferation; IL-6, an inflammatory cytokine; and VEGF-A, an angiogenesis marker, were significantly down-regulated in the BPH group that were treated with crocin. Conclusions: The present study indicates that crocin can effectively prevent the development of experimentally induced BPH through inhibition of prostatic cellular proliferation, inflammation, and angiogenesis.