The thymus is the most important central immune organ of mammals which determines the aging of immune system. It is the major site of T cell maturation where extensive proliferation and differentiation occur. Age-related deterioration of the thymus can affect the function of peripheral T cells, which inevitably impairs the responsiveness of immune system to foreign antigens, leading to delayed clearance of pathogens. This also increases the risk of elderly people suffering from cancer, autoimmune diseases and infections diseases caused by viruses, bacteria and other pathogens. This review presents the latest information on the role of transcription factors and cytokines in the progress of age-related thymic involution. We also review the studies on the regulation of the functional recovery of thymus.