Type 1 diabetes (T1D) is a chronic autoimmune disease caused by proinflammatory autoreactive T cells that mediate the selective destruction of insulin-producing beta cells via both direct and indirect mechanisms. Many immune cells and proinflammatory cytokines are involved in the pathogenesis of autoimmune diabetes. Immune intervention is effective for the prevention and treatment of T1D by blocking the autoimmune assault to beta cells. The non-structural protein 1(NS1) of influenza A viruses is a non-essential virulence factor encoded on segment 8 that has multiple accessory functions, including suppression of innate immunity and adaptive immunity, inhibition of apoptosis and activation of phosphoinositide 3-kinase (PI3K). This research investigated whether the expression of NS1 can prevent and treat diabetes mellitus induced by Streptozotocin (STZ). The NS1 expressing plasmid pEGFP-C2/NS1 was constructed and injected intramuscularly to both thighs of mice. Its effect on mice was observed. Intramuscular delivery of pEGFP-C2/NS1 resulted in reduction in hyperglycemia and diabetes incidence, with an increase in insulin. pEGFP-C2/NS1 could also increase glycogen and regulated serum cytokine levels. In addition, by comparison to the mice treated with empty vector pEGFP-C2, ameliorative insulitis was observed in the mice treated with recombinant plasmid pEGFP-C2/NS1. This result suggests that the expression of NS1 is effective for the prevention and treatment of diabetes mellitus induced by STZ in a mouse model. (C) 2012 Elsevier Inc. All rights reserved.