OBJECTIVE: To study the protective mechanism of flavoxate on prostatic hyperplasia in model rats. METHODS: The rats were randomly divided into sham operation group, model group and flavoxate high-dose and low-dose groups (80, 40 mg/kg), with 8 rats in each group. Except for sham operation group, those groups were emasculated and given sterandryl to induce BPH model. They were given relevant medicine intragastrically 1 h after administration of sterandryl, once a day, for consecutive 4 weeks. Sirius red and Masson staining were used to detect the precipitation of collagen in prostate; immunohistochemistry was used to detect the expressions of prostatic type Ⅰ collagen, FN and E-cadherin; ELISA assay was used to determine the levels of SOD, GPx, MDA, EGF and VEGF in prostate. qPCR assay was used to detect the levels of miR-21 and TGF-β1. RESULTS: Compared with the sham operation group, the prostatic collagen was accumulated; prostatic index, the expression of FN, MDA content and levels of VEGF, EGF, miR-21 and TGF-β1 were increased (P<0.05); the expression of E-cadherin, and the activity of SOD and GPx were decreased (P<0.05). Compared with model group, the precipitation of prostatic collagen was decreased; prostatic index, the expression of FN, MDA content, the levels of VEGF, EGF, miR-21 and TGF-β1 were decreased in flavoxate high-dose and low-dose groups (P<0.05); while the expression of E-cadherin and the activity of SOD and GPx were increased (P<0.05). CONCLUSIONS: Flavoxate can inhibit BPH, the mechanism of which may associated with down-regulating the expressions of miR-21 and TGF-β1, inhibiting oxidative stress and angiogenesis and improving epithelial-mesenchymal transition.