Objective To investigate age-related changes in the expression of human leukocyte antigen-DR (HLA-DR) in peripheral blood mononuclear cells (PBMCs) and levels of cytokines secreted by PBMCs. Methods A total of 352 individuals who underwent physical examinations in our hospital were stratified into four groups based on age: group A, n = 120, age 20-69 years; group B, n = 85, age 70-79 years; group C, n = 98, age 80-89 years; group D, n = 49, age 90-102 years. Expression of HLA-DR in PBMCs was detected with flow cytometry. In addition, 10 individuals from each group were randomly selected, and their PBMCs were isolated and subsequently used for determining the levels of TNF-α, IL-6 and IL-10 by ELISA before and after LPS stimulation. HLA-DR expression and cytokine levels were compared between the different age groups. Results HLA-DR expression was significantly different between A, B, C, and D groups (F = 159.712, P = 0.000), and it increased in an age dependent manner (r = 0.744, P = 0.000). No significant difference was found in TNF-α, IL-6 and IL-10 levels in PBMCs before LPS stimulation between group A, B, C and D (P＞0.05), while, their levels increased significantly after LPS stimulation (P＜0.05). Compared with group A, TNF-α and IL-6 levels decreased, and the IL-10 level increased significantly(P ＜0.05) in group B, C and D after LPS stimulation. Conclusion Expression of HLA-DR increases in an age-dependent manner in human PBMCs, indicating an age-related change of immunological function. There is no significant difference in the levels of TNF-α, IL-6 and IL-10 secreted by PBMCs before LPS stimulation, while after LPS stimulation, the TNF-α and IL-6 levels decrease and IL-10 level increases significantly in individuals more than 70 years old.