Neuro-inflammation has been proposed as a causative factor of neurological diseases and disorders during the ageing process. The senescence-accelerated mouse (SAM) is known to be a good murine model for accelerated aging. The aim of this research was to investigate the effect of aging on inflammation in brains obtained from SAMP8 and SAMR1 male mice and the influence of chronic exogenous administration of melatonin. Animals of 2 (young) and 10-11 months of age (old) were used. The influence of the administration of melatonin in the drinking water for one month at two different dosages (1 and 10 mg/kg/day) on brains of old mice was studied. The levels of pro/anti- inflammatory cytokines were studied by ELISA. During ageing the level of IL 2 was increased in brain of both mice strains as compared to young animals. However, the level of this cytokine was higher in old SAMP8 as compared with SAMR1 of the same age. The levels of TNF-α and IL 6 were also increased significantly in brains of SAMP8 and SAMR1 old male mice as compared to young animals. Melatonin treatments in both doses were able to decrease levels of IL2, TNF-α and IL 6 in both strains of mice. The levels of anti-inflammatory cytokines (IL 4 and IL 10) were decreased in the brain of old SAMP8 male as compared with young mice. Interestingly, the levels of these cytokines did not show differences between young and old SAMR1 male animals. Differences between strains were observed with higher levels of anti-inflammatory cytokines in old SAMR1 as compared with SAMP8 animals of the same age. After chronic treatment with melatonin a significant increase in levels of IL 4 and IL 10 were detected in group of old SAMP8, but not in the case of SAMR1 male mice. We have demonstrated that in brain of old SAMP8 mice the levels of pro-inflammatory cytokines were increased, but the anti-inflammatory were decreased as compared with SAMR1. Increases in pro-inflammatory cytokines in the brain may be involved in the age-related neural dysfunction and/or learning deficiency in SAMP8 mice. Melatonin treatment was able to improve the dysbalace of neuro-inflammation in brain.