Taken together, the data above convincingly indicate the crucial role of H2S as a potent antioxidant molecule that, at low concentrations, induces protective actions exploited through the redox modulation of the Nrf2 vitagene signaling pathway which may provide a novel potential therapeutic approach to confer resilience against oxidative stress, inflammation as well as apoptosis during pathological conditions such as diabetes and related complications. This evidence concerns the gene NFE2L2 and diabetes mellitus.