Parasitic helminth infections are characterized by eosinophilia and markedly elevated levels of circulating antigen-nonspecific immunoglobulin E (IgE), responses from which concern helminth protection. We previously purified a factor from Dirofilaria immitis that induces antigen-nonspecific IgE in mice and rats. Recombinant DiAg (rDiAg) has various biological activities. It is also known that parasitic helminth infection generates tremendous Th2 responses. The nonobese diabetic (NOD) mouse spontaneously develops Th1 cell-dependent autoimmune diabetes. Here we investigated the effects of rDiAg on the initiation and progression of this disease. rDiAg treatment of 6-week-old NOD females (the age at which insulitis typically begins) completely prevented insulitis and diabetes. Thus, rDiAg impaired the islet Ag-specific Th1 cell response in vivo, and the prevention of diabetes by rDiAg was associated with switching of the response from a Th1 to a Th2 profile. Since rDiAg clearly prevented insulitis by inhibiting the development and further accumulation of pathogenic Th1 cells to islets of Langerhans, we conclude that DiAg is a native Th2 inducer in filarial helminth and that Th1 responses are required for early events in the development of spontaneous autoimmune diabetes. In conclusion, the presence of parasitic helminth infections may play an important role as an immunomodulator in some autoimmune diseases or allergies.