The macroglobulin family represents a group of universal regulators involved into control of the inflammatory response to external and internal pathogens. Alpha-2-macroglobulin (MG), the major protein in the family, has 3 different binding sites and high affinity to an endocytosis receptor that allows MG to participate in recognition and phagocytosis of the foreign agents. The macroglobulin family proteins are most powerful apoptosis inhibitors: they bind autoaggressive hydrolases accumulating during inflammation. MG is the main transporter of cytokines and growth factors controlling the inflammatory response. At the same time, the macroglobulins are negative reactants of an acute phase of inflammation and the decrease of their synthesis at later stages is necessary for stimulation of collagenosis processes, coagulation, activation of thymulin, stimulating NK. At septic inflammation binding of macroglobulins to exotoxins can localize inflammation, and initiate systemic inflammatory response. Macroglobulin damage sharply reduces their subsequent utilization; this provokes accumulation of makroglodulin-proteinase complexes in biological fluids and may cause immune inflammation.