Here, we showed that GCN2 inhibition decreased 4-HNE and 3′-NT levels and increased the protein expression of NRF2, NQO-1, and HO-1 in the livers of T2D mice, indicating that the protective effect of GCN2 inhibition in T2D mice was also associated with activation of the Nrf2 pathway and suppression of hepatic oxidative stress. Here, EIF2AK4 is linked to type 2 diabetes mellitus.