Objective: This study aimed to investigate the impact of apolipoprotein E 4 (APOE4) gene polymorphisms on the expressions of inflammatory factors and the progression of Alzheimer's disease (AD). Methods: A total of 185 AD patients (the case group, 130 cases from the Han ethnic group and 55 cases from the She ethnic group) and 190 healthy individuals (the control group, 130 cases from the Han ethnic group and 60 cases from the She ethnic group) were recruited for our study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was conducted to detect APOE4 genotype and allele frequency. Enzyme-linked immunosorbent assay (ELISA) was used to determine the expressions of inflammatory factors in plasma. Results: In both Han and She populations, the frequency of epsilon 3/4 and epsilon 4/4 genotypes and the epsilon 4 allele was significantly higher in the case group than that in the control group. epsilon 3/4 and epsilon 4/4 genotypes and the epsilon 4 allele were the risk factors for AD. In both Han and She populations, the epsilon 2/4, epsilon 3/4 and epsilon 4/4 carriers showed increased levels of TNF-alpha, IL-6, and IL-1 beta when compared with the epsilon 2/2 + epsilon 2/3 + epsilon 3/3 carriers. The TNF-alpha, IL-6, and IL-1 beta levels were higher in the epsilon 4/4 carriers than those in the epsilon 2/4 and epsilon 3/4 carriers, and epsilon 2/4, epsilon 3/4 and epsilon 4/4 carriers in the case group exhibited increased levels of TNF-alpha, IL-6, and IL-1 beta when compared with the control group (P < 0.05). Logistic regression analysis indicated that the epsilon 3/4 genotype and TNF-alpha, IL-6, and IL-1 beta levels were associated with the susceptibility to AD in the Han population, while epsilon 3/4 and epsilon 4/4 genotypes and TNF-alpha, IL-6, and IL-1 beta levels were related to the susceptibility to AD in the She population. Conclusions: The APOE4 epsilon 4 allele may enhance susceptibility to AD and promotes the expressions of inflammatory factors in AD.