Background: Aging is associated with attenuation of immune responses. Studies show that old people are vulnerable to infectious diseases such as influenza. α-Tocopherol as an immunomodulator affects immune responses. In the present study, the effect of α-tocopherol, on lymphocyte responses i.e. interferon-gamma (IFN-γ), Tumor Necrosis Factor-alpha (TNF-α), and nuclear factor-κB (NF-κB) in elderly individuals was evaluated. Materials and Methods: Heparinized blood samples were prepared from 10 elderly individuals (n=10, age >80 years) as the experimental group and 10 young individuals (n= 10, 20-40 years) as the control group. The separated Peripheral Blood Mononuclear Cells (PBMCs) of aged and young individuals were used for treatment with 2 μg/mL of α-tocopherol and 2 μg/mL of Purified Protein Derivative (PPD) after 12 and 24 h incubation period. After isolation of total RNA and synthesize of cDNA, the gene expressions of IFN-γ, TNF-α, and NF-κB were evaluated by real-time PCR method. β-Actin gene was considered as the internal control gene. Results: Results showed that treatment with α-tocopherol increased the IFN-γ expression in old and young lymphocyte groups. The mRNA level of NF-κB increased in the PPD group after 12 h in both old and young groups (p <0.05). There were no alterations in TNF-α expression in both groups. Conclusion: It seems that α-tocopherol is effective in the promotion of cytokine responses in old individuals and may be useful as a supplement for improving the immune system of elderly people.