We determined a protective action of probucol (4,4'-[isopropylidenedithio]bis[2,6-di-tert-butylphenol]) on the reduction of serum immunoreactive insulin (IRI) levels by recombinant human interleukin-1 beta (IL-1) in adrenalectomized rats. IL-1 reduced the serum IRI levels 4 h after injection in rats fed a standard diet. However, IL-1 failed to inhibit serum IRI levels in rats fed a diet containing 1% probucol. In contrast, IL-1 decreased plasma glucose levels in both groups. Although IL-1 reduced plasma prostaglandin (PG) E2 levels in standard diet-fed rats, IL-1 did not affect plasma PGE2 levels in the animals fed the probucol-containing diet. The present study suggested that the free radical scavenger action of probucol can block the IL-1 effect on serum IRI levels.