T-2 toxin is an inevitable environmental and grain pollutant, which can cause kidney damage, but the mechanism is not clear. In this study, male mice were administered with T-2 toxin at 0, 0.5, 1.0, 2.0 mg/kg body weight (BW) for 28 days. We found that T-2 toxin induced renal structural damage, downregulated BW and kidney coefficient, impaired renal function accompanied by oxidative stress and apoptosis. Meanwhile, T-2 toxin increased nuclear Nrf2 protein expression and the mRNA expressions of its downstream target genes. The correlation analysis indicated that apoptosis and Nrf2 pathway were positively correlated with oxidative stress. These results suggested that the nephrotoxicity of T-2 toxin in mice caused by oxidative stress-mediated apoptosis is related to Nrf2 pathway.