An ongoing need exists to identify combinations of therapeutic agents having a substantial potential for preserving residual beta cell function in persons with new-onset type 1 diabetes (T1D). Prior to clinical testing, most treatment regimens pass through a phase of evaluation in animal models, especially the NOD mouse model of T1D. While such preclinical results can be important, they often are the product of relatively small animal numbers achieved in a single site. In order to prioritize candidate combinations of agents, the Immune Tolerance Network (ITN) and the JDRF developed a preclinical, multi-center consortium to test the efficacy for specific combinations of therapeutic agents to reverse new-onset disease in NOD mice. This program is a coordinated effort to conduct standard operating procedure (SOP)-directed, prospective studies in NOD mice using common reagents at four different participating institutions. As such, this enterprise has the potential to both determine the reproducibility of treatment regimens among different NOD colonies and to enable the numerical powering of studies, which is often challenging at a single site. The primary goal of this approach is to verify the efficacy and safety of synergistic combinations of therapeutic agents with direct potential for clinical application. This innovative translational approach is intended to produce robust preclinical data as a tool to prioritize combinational therapeutic regimens for consideration in phase I/II clinical trials in settings of T1D.