The effect of thymectomy performed at weaning (3 weeks) and at 6–7 weeks of age on the incidence of diabetes was examined in the non‐Obese diabetic (NOD) mouse, a spontaneous model of immunologically mediated insulin‐dependent diabetes similar to human type I diabetes. When performed at weaning, thymectomy led to a dramatic increase in the incidence of diabetes in NOD females in comparison to sham‐thymectomized animals. Conversely, no change in the incidence of the disease or the expression of insulitis was noted when thymectomy was performed in NOD males. When delayed beyond 6–7 weeks of age, thymectomy had no effect on NOD males and females. Flow cytometry analysis of spleen cells from intact mice and mice thymectomized at weaning or at 6–7 weeks of age demonstrated a significant depletion of the T cell subsets in both groups of thymectomized animals. These results indicate that the onset of diabetes in NOD mice is submitted to thymic regulation and that the T cell depletion induced by thymectomy at weaning accelerates the disease, an effect possibly due to the loss of some T cell‐dependent suppressor mechanisms.