We review the critical roles of peroxiredoxin (PRDX) 4 in inflammatory diseases. The PRDX family, a new family of proteins with an antioxidative function, is ubiquitously synthesized and abundantly identified in various organisms. The function of these enzymes, which include at least six distinct PRDX genes expressed in mammals, still remains unclear. Especially, in contrast to the intracellular localization of other family members, PRDX4 is the only known secretory form located in the extracellular space and exerts its protective function against oxidative damage by scavenging reactive oxygen species in the vascular vessels. To date, however, it is not clear whether or how PRDX4 expression affects various diseases in vivo. More recently, we generated human PRDX4 (hPRDX4) transgenic (Tg) mice, and, for the first time, established a type 1 diabetes mellitus model induced by a single high dose of streptozotocin on Tg mice. Our published data demonstrate that streptozotocin-treated Tg mice, which overexpress hPRDX4 in pancreatic islets, can protect pancreatic beta-cells against streptozotocin-induced injury (insulitis) by suppressing increased oxidative stress and inflammatory signaling activation. These observations indicate that Tg mice could become a useful animal model to study the relevance of oxidative stress to inflammation, and that a specific accelerator of PRDX4 might prove to be a potential therapeutic agent for ameliorating various chronic inflammatory diseases.