HLA-DR, a major histocompatibility complex, MHC class II, is involved in several autoimmune conditions, disease susceptibility and disease resistance. Here, we investigate the impact of different age individuals on HLA-DR expression on peripheral blood mononuclear cells (PBMCs) induced by lipopolysaccharide (LPS). The results indicate that HLA-DR expression on PBMCs in the population aged above 70 years significantly increased as compared with that in the lower-age groups by flow cytometry analysis (B–D; r = 0.690, P = 0.000265). In addition, followed by LPS stimulation, the levels of cytokine TNF-α, IL-6 and IL-10 secretion by allogeneic T lymphocytes from different age groups (A–D) were significantly increased (P < 0.05). Notably, levels of TNF-α and IL-6 were significantly reduced in groups B, C and D as compared with group A (P < 0.05), whereas levels of IL-10 increased (P = 0.012). However, no significant difference in PBMC-secreted TNF-α, IL-6 and IL-10 levels was observed among groups A, B, C and D (P > 0.05) before LPS stimulation. We firstly present data showing an age-dependent increase in HLA-DR expression in the population aged above 70 years and the individual with aged above 70 years has reduced the secretion of inflammatory mediators (TNF-α and IL-6) by PBMCs and increased the secretion of anti-inflammatory cytokine (IL-10) after LPS stimulation in vitro. The better understanding of HLR–DR expression on human PBMCs in aged individuals and its relation to the host cellular immunity would provide important insights into the immunity of aged individuals and particularly, in elderly patients with sepsis.