The pathophysiology of GVHD shows that it has different phases. In first phase i.e., afferent phase, damage to host tissue occurs. In second phase i.e., Induction and expansion phase, donor T cells are triggered and activated by recipient and donor APC as well as the inflammatory cytokines. Activated T cells produce IL-2 and IFN-γ (or Th1 response). Allogeneic immune response is amplified by IL-2, which activates more T cells and natural killer cell responses, triggering macrophages to release TNF-α and further inflammation damages skin and gut. The third phase i.e., effector phase, is characterized by cytotoxic damage against host cells by activated donor T-cell-mediated through Fas-Fas ligand interaction, perforin-granzyme and TNF-α. The latter has a central role in the pathophysiology, stimulating cytokine production (IL-1, IL-6, IL-10, IL-12 and TNF-α). This dysregulation leads to the clinical manifestations of acute GVHD.