Some physiological measures change with age, but the existence of age-related disorders such as type 2 diabetes raises questions about which patterns reflect progressive pathology and which are manifestations of aging. Here we report a retrospective investigation of age-related physiological changes in rhesus monkeys that developed diabetes (D group, n = 65) or exhibited healthy aging (N group, n = 88). Data were available on clinical chemistries, hematology, glucose tolerance, and insulin sensitivity based on oral and intravenous glucose tolerance tests and euglycemic, hyperinsulinemic clamp assessments. Individuals contributed data for an average of 7.6 years, when they were between 5 and 30 years of age. Only glucose disappearance rate, insulin sensitivity rate, and high density lipoprotein levels changed significantly with age in the nondiabetic group. In the diabetic group, significant decreases in glucose tolerance were evident by middle age (age 14 y), and fasting insulin first increased before diabetes was diagnosed, and then declined with advancing age.