Studies of the relationship between Alzheimer's disease (AD) and polymorphism in the promoter region of Interleukin 6 (IL-6) -174 G/C have reported inconsistent results. To assess the association between IL-6 -174 G/C promoter polymorphism and AD risk, a meta-analysis containing 3,101 AD cases and 3,860 controls from 18 case-control studies was performed. There were 16 studies involving Europeans and 2 studies involving non-Europeans. The combined results showed significant differences in recessive model [CC versus GC + GG, odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.54-0.90] and heterozygote comparison (CC versus GC, OR = 0.76, 95% CI = 0.60-0.96) on the basis of all studies. On subgroup analysis by ethnicity, similarly significant differences in recessive model (CC versus GC + GG) were found in both Europeans and non-Europeans, but significant difference in heterozygote comparison (CC versus GC) was found only in non-Europeans. In conclusion, there were statistically significant differences in genotype distribution of IL-6 -174 G/C between AD cases and controls in recessive model (CC versus GC + GG). Genotype CC of IL-6 -174 G/C could decrease the risk of AD. Further studies with large sample size, especially in subgroup analysis, should be done.