Diosgenin, as an essential natural steroidal saponin, can be extracted from numerous sources, primarily from fenugreek. It is an important raw material for the synthesis of steroid hormone drugs. It exhibits antitumor, anti‑inflammatory, antioxidation and several other significant pharmacologic actions, and is of high pharmaceutical value. In the present study, the activities and underlying mechanisms of dioscin in the inhibition of ischemic stroke in rats were investigated. Inflammatory responses wer analyzed using ELISA kits and caspase‑3 and caspase‑9 activity was analyzed using Caspase‑3 and caspase‑9 activity kits. Western blot analysis was used to measure Toll‑like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor‑κB (NF‑κB), transforming growth factor‑β1 (TGF‑β1), high‑mobility group protein 1 (HMGB‑1), interleukin‑1 receptor‑associated kinase 1 (IRAK1), and tumor necrosis factor receptor‑associated factor 6 (TRAF6) protein expression. Dioscin inhibited infarct volume and neurological scores in the ischemic stroke rat model. The results demonstrated that dioscin reduced inflammatory responses, and suppressed the expression of TLR4, MyD88, NF‑κB, TGF‑β1, HMGB‑1, IRAK1, and TRAF6 in the rat ischemic stroke model. Taken together, these findings suggested that dioscin inhibited ischemic stroke‑induced inflammation through inhibition of the TLR4/MyD88/NF‑kB‑induced inflammation the rat model, which provided novel insights into the mechanisms underlying the effect of dioscin as an anti‑inflammatory candidate for the treatment of ischemic stroke in in the future.