Aging is associated with an increase in oxidative stress and inflammation. The aim of this study was to investigate the effect of aging on various physiological parameters related to inflammation in livers obtained from two types of male mice models: Senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant (SAMR1) mice, and to study the influence of the administration of melatonin (1mg/kg/day) for one month on old SAMP8 mice on these parameters. The parameters studied have been the mRNA expression of TNF-α, iNOS, IL-1β, HO-1, HO-2, MCP1, NFkB1, NFkB2, NFkB protein or NKAP and IL-10. All have been measured by real-time reverse transcription polymerase chain reaction RT-PCR. Furthermore we analyzed the protein expression of TNF-α, iNOS, IL-1β, HO-1, HO-2, and IL-10 by Western-blot. Aging increased oxidative stress and inflammation especially in the liver of SAMP8 mice. Treatment with melatonin decreased the mRNA expression of TNF-α, IL-1β, HO (HO-1 and HO-2), iNOS, MCP1, NFκB1, NFκB2 and NKAP in old male mice. The protein expression of TNF-α, IL-1β was also decreased and IL-10 increased with melatonin treatment and no significant differences were observed in the rest of parameters analyzed. The present study showed that aging was related to inflammation in livers obtained from old male senescence prone mice (SAMP8) and old male senescence resistant mice (SAMR1) being the alterations more evident in the former. Exogenous administration of melatonin was able to reduce inflammation.