The importance of the role of inflammation has been suggested in the pathogenesis of Alzheimer's disease (AD). Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may modulate the progression of the disease through the inhibition of the action of pro-inflammatory cytokines. In this study, three polymorphisms in the regulatory region of the IL-10 gene (−1082, −819 and −592) in 95 Chinese AD patients and 117 age-matched healthy Chinese subjects were investigated. We found that among the Chinese population, the A and C alleles at the −592 position are strongly linked to the T and C alleles at the –819 position, respectively. A strong association with AD was found for these two IL-10 polymorphisms, which are in complete linkage disequilibrium (−592C and −819C), and the odds ratio of AD is 4.03 (95% CI 1.23–13.23; p = 0.011). The functional significance of the IL-10 genotype was further supported by the significant association between plasma IL-10 concentrations and genotypes that were found in an independent sample of 160 healthy male volunteers. No interaction effect between the ApoE and IL-10 genotypes is found. Therefore, we concluded that the functional polymorphisms of the IL-10 gene act as a risk factor for AD.