We investigated the effects of probucol on endothelial damage induced by exogenous free radicals and on activity of nitric oxide (NO).The results demonstrated that rabbit aortic rings incubated with xanthine(X,100 μmolL-1) and xanthine oxidase(XO,100 U·L-1) for 30min showed weak response to acetylcholine and that cultured bovine aortic endothelial cells incubated with X-XO for 30 min showed decrease of NO release and increase of malondialdehyde content.Probucol (40, 80 and 120 μmol·L-1) could protect endothelial cells from injury due to X-XO in a concentration-dependent menner, Inactivator of NO oxidized hemoglobin(OHb, 100μmol·L-1), not synthesis inhibitor of NO NG-nitro-L-arginie(NG-L-Arg,100 μmol·L-1), could abolish the effect of probucol. In the inhibitive experiment of NO synthesis and effect, we observed that the acetylcholine -induced relaxation ratio of aortic rings was reduced by NG-L-Arg, OHb and NO antagonist methylene blue(MB,100 μmol·L-1).Probucol 80 μmol·L-1 could contend with the relaxing inhibition of O Hb and MB not NG-L-Arg. Our data indicate that probucol can protect endothelial cells from damage due to free radicals. The mechanism of such protection may be partly associated with the maintenance of NO activity.