In the non-obese diabetic (NOD) mouse model of Type 1 Diabetes (T1D), genetically identical mice raised in the same environment develop diabetes at different rates. While much is known about the immune responses in this strain which predispose to T1D, there are no known predictors of disease progression. Definition of such markers in mice would aid understanding of the mechanism of progression and may be translatable to children at risk. Since peripheral blood (PB) is readily accessible, we analysed serial PB samples in NOD mice over the T1D prodrome then scored pancreatic insulitis at 14 weeks or determined age of diabetes onset. Expression of TNF mRNA in the pre-diabetic period was negatively associated with insulitis score at 14 weeks, but not with age of diabetes onset. We therefore profiled gene expression in PB of 10-week NOD mice and determined age of diabetes onset. NOD mice developing diabetes before 17 weeks of age could be distinguished from late onset and non-diabetics by a signature of downregulated PB genes. Expression of a gene in PB at 10 weeks correlated with age of diabetes onset. In a clinical cohort of first-degree relatives and T1D patients, the expression of this gene was significantly higher in islet antibody-negative than antibody-positive or diabetic individuals. These PB predictive markers facilitate identification of pre-clinical functional immune phenotypes in NOD mice destined for accelerated diabetes onset, and for validation in human cohorts of progressors and non-progressors to T1D.