The platelet-activating factor inhibitor BN50730, a hetrazepine, was injected intraperitoneally daily from 30 days of age into diabetes-prone BB rats. While 96% (22123) Tween 80 injected control rats developed diabetes, 0.05 mg/kg BN50730 decreased the frequency to 72% (17/24;n.s.) and 0.5 mg/kg to 56% (14125;p<0.01). Mean onset age in controls was 81±9 days (mean±SD), but BN50730 delayed onset to 87±15 days in the low and 93±12.days (p<0.01) in high dose rats. The relative degree of insulitis was reduced in both low (p<0.01) and high (p<0.05) dose treated groups. Serum insulin in young prediabetic controls decreased from 84±34μU/ml to 38±20 in the 22 rats developing diabetes (p<0.001). Serum insulin in BN50730-protected compared to unprotected rats was 114±49 and 32±22 (p<0.001) in the low, and 91±4 6 and 21±15 (p<0.001)μU/ml in the high dose group, respectively. Increased serum insulin correlated with preserved isletβcells and decreased insulitis. Treatment did not affect thyroiditis. Thus, platelet-activating factor may be involved in insulitis pathogenesis and platelet-activating factor inhibitors may decrease autoimmuneβcell destruction.