Thymosin alpha 1 (Tα1), a 28-amino-acid peptide, was first described and characterized from calf thymuses in 1977. This peptide can enhance T cell, dendritic cell (DC), and antibody responses, modulate cytokine and chemokine production and block steroid-induced apoptosis of thymocytes. Due to its pleiotropic biological activities, Tα1 has gained increasing interest in recent years and has been used for the treatment of various diseases in clinic. Many studies have been performed to identify the immunoregulatory activity of Tα1 in vitro and in vivo. Evidence has shown that Tα1 increased the efficiency of T cell maturation, stimulated precursor stem cell differentiation into the CD4+7/CD8+ T cells, and balanced CD3/CD4+/CD8 T cells of peripheral blood mononuclear cells (PBMCs). By stimulating natural killer (NK) cells and cytotoxic lymphocytes (CD8+ T cell), Tα1 could directly kill virally infected cells by activating dendritic cells (DCs). Tα1 was able to protect immunocompromised mice from death caused by aspergillosis. Tα1 stimulated a significant increase of IL-2 and led to a decrease in the Th2 cytokines such as IL-4 and IL-10 in patients with chronic HCV. Tα1 remarkably decreased the impact of severe acute pancreatitis by harming serum levels of IL-1β and tumor necrosis factor-alpha (TNF-α). Tα1 also upregulated specific cytokine receptors such as the high-affinity IL-2 cytokine receptor.