To analyze the role of Nrf2-ARE signaling pathway in the regulation of the acute phase of pilocarpine-induced epilepsy in juvenile rats by Tatarinow Sweetflag Extract (TSE). One hundred and twenty SPF-grade Wistar male rats were were divided into five groups by random number table method, namely, normal group, model group, low-dose TSE group, high-dose TSE group, low-dose TSE + Nrf2 inhibitor Brusatol group (low-dose TSE + BRU group), and high-dose TSE + Nrf2 inhibitor Brusatol group (high-dose TSE + BRU group), with 20 rats in each group. The success rate of modelling in the model group, low-dose TSE group, high-dose TSE group, low-dose TSE + BRU group, high-dose TSE + BRU group were 60.00% (12/20), 65.00% (13/20), 65.00% (13/20), 70.00% (14/20), and 70.00% (14/20), respectively, showing no significant difference (P > 0.05). The latency and incidence of class IV and V, discharge amplitude as well as frequency of rats in the low- and high-dose TSE groups were lower than those in the model group (P < 0.05); the lipid peroxide and malondialdehyde concentrations in hippocampal tissues in the low- and high-dose TSE groups were lower than those in the model group (P < 0.05); The Nrf2, NQO-1 and HO- 1 protein and mRNA expression levels were increased in the low- and high-dose TSE groups compared with the model group (P < 0.05). The therapeutic effect of TSE in rats with acute epilepsy was satisfactory, and its mechanism of action may be related to activation of Nrf2-ARE signaling pathway to reduce the degree of oxidative stress.