This study describes the morphology, time appearance, persistence, and immunomodulation of extraislet infiltration in the nonobese diabetic (NOD) mouse pancreas. Female NOD mice were subdivided into two groups: untreated, killed at week 5 (n = 8), 10 (n = 8), or 21 (n = 8) of life; ganglioside treated (200 mg/kg body wt/day given from week 4 until week 21 of life, plus complete Freund's adjuvant at week 4), killed at week 10 (n = 6), 21 (n = 6), or 25 (4 weeks after the end of the ganglioside treatment; n = 6). Mononuclear elements were seen around small ductules located both in the vicinity of and far from the islets. Larger ducts were completely devoid of inflammation, thus evidencing that periductulitis is specific only to small ductules. Moreover, an exocrine focal pancreatitis was seen along septa and may demonstrate that macrophage activation takes place throughout the pancreatic connective tissue. Immunomodulation determines some suppression of insulitis; nevertheless, after treatment withdrawal, a reinfiltration occurs both within and outside the islets.