Background: Immunologic destruction of pancreatic p-ce11 plays a primary role in pathogenesis of IDDM. According to reeent studies, the oxygen free radical liberated from cytokines is closely associated with the final pathway of p-cell destruction. Blocking this path- way by drugs and other measures will be able to prevent. P-cell destruction and to delay the onset of overt diabetes. Many authors reported that oxygen free radical scav- engers effectively prevent the -cell destruction in ani- mal model of IDDM. However their precise mechanism of action or dosage of drugs were not known. 53ethod: To evaluate the effects f combined treat- ment of high and low dose nicotinamide (NA) with insulin on multiple low dose streptozotocin induced diabetic (LDSD) mice, 160 LDSD mice (Charles-River CD-1 male mice) were divided into 6 groups and the then treated with high (500 mg/kg), low dose (50mg/kg) nicotinamide, iinsulin and both drugs for 7 weeks. During the experir.nental period, the blood glueose level and the bady weight were measured and on the 56th experimental day, the mice were sacrificed and pancreatic sections were obrmived to determine the frequency and the severity of insulitis in each experimental group. Rewdta: The results were as follows; 1) In insulin treated groups, body weights of mice increased, especially more significant in low dose nicat;namide and insulin combined group. 2) Blood glucose leveis in all treated groups were significantly lower compared to control group but there was no definite correletion between the severity of insulitis and blood giueose level. 3) All treated groups showed statistically significant low frequency of insulitis compared to control group. The hiigh dose nicotinamide and insulin combined group showed the most effective prevention of 9-cell destruction and the second favorabIe result was demonstrated in lov dose nicotinamide and insulin combined group. Conelusiions: From t4e above results, it was shown that the rombination treatment of nicotinamide and insulin more effectively alleviates the progression of LDS induced insulitis than single treatment but there was no definite correlation between the severity of insuIin and the blood glucose level. Low dose nicotinamide had the same preventive effect on p-cell destruction in LDSD mice as high dose, and early insulin treatment also had the sarne favorable effect as nicotinamide had.