The deleterious effects of ethanol in senescence-accelerated prone 8 mice (SAMP8) and the protective role of nicotinamide (NAM) against ethanol-induced liver injury were examined. The mice were orally administered 2 g ethanol/kg BW and 200 mg or 500 mg NAM/kg BW three times/week for 10 weeks. Results showed that ethanol elevated activity of alanine aminotransferase (ALT) significantly. Ethanol also enhanced the formation of malondialdehyde (MDA) and protein carbonyls in the liver, whereas ethanol treatment resulted in significantly lower activity of hepatic glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD). Hematoxylin and eosin staining indicated moderate to severe fatty infiltration but not fibrosis. Administration of high NAM (500 mg/kg BW) led to markedly decreased levels of hepatic MDA, protein carbonyls, fatty infiltration and the activity of ALT, and increased activity of GPx, catalase and SOD in the ethanol-fed group. Thus, using SAMP8 as animal model for ethanol-induced liver injury in the aged mice, this study demonstrates that NAM is effective in protecting such damage.