Immune phenotyping provides insight into disease pathogenesis and prognostic markers. Trajectories from age of 4 to 36 weeks were modeled for insulin autoantibodies and for leukocyte subpopulations in peripheral blood from female NOD (n = 58) and NOR (n = 22) mice. NOD mice had higher trajectories of insulin autoantibodies, CD4(+) and CD8(+) T lymphocytes, B lymphocytes, IgD(+)IgM(-) B lymphocytes, and NK cells and lower trajectories of CD4(+)CD25(+) T lymphocytes, IgM(+) B lymphocytes, granulocytes, and monocytes than NOR mice (all p < 0.001). Of these, only the increased IAA trajectory was observed in NOD mice that developed diabetes as compared to NOD mice that remained diabetes-free. Therefore, the profound differences in peripheral blood leukocyte proportions observed between the diabetes-prone NOD mice and the diabetes-resistant mice do not explain the variation in diabetes development within NOD mice and do not provide markers for diabetes prediction in this model.