The anti-inflammatory effects of two esters of a-tocopherol (α-TOH), all-rac-α-TOH acetate (DL-α-TOA) and RRR-α-TOH succinate (D-α-TOS), on broilers repeatedly challenged with lipopolysaccharide (LPS) were investigated. Three hundred and twenty 1-d-old broiler chicks were allotted into four treatment groups and fed on a control diet (30 mg/kg DL-α-TOA) or diets containing 10, 30, 50 mg/kg D-α-TOS. Half of the birds from each treatment group were challenged with 0·9% NaCl solution or LPS (250 μg/kg body weight) at 16, 18 and 20 d of age. The results indicated that the pretreatment of birds with 50 mg/kg D-α-TOS markedly reduced serum PGE₂ secretion and increased the concentrations of serum or hepatic α-TOH. When LPS-challenged birds were pretreated with 30 or 50 mg/kg D-α-TOS, the increases of plasma and splenic concentrations of interferon-γ, IL-1ß, IL-2, IL-6, IL-4 and IL-10 were dramatically attenuated. Also, a significant decrease of hepatic reactive oxygen species (ROS) and hepatic or splenic phosphokinase C (PKC) activities was found in birds pretreated with 30 or 50 mg/kg D-α-TOS. Furthermore, D-α-TOS inhibited the activation of NF-κB by preventing the degradation of inhibitory-κBα. In conclusion, D-α-TOS is able to prevent LPS-induced inflammation response in vivo. The beneficial effect may depend on suppressing the secretion of various plasma and splenic inflammatory mediators through inhibiting NF-κB activation and by blocking ROS signalling, in which PKC may play an assistant role.