We studied the effect of myofibrils on proliferation and differentiation of myoblasts cocultured with macrophages as well as the effect of incubation of macrophages with myofibrils on the expression by macrophages of the compounds that are cytokines for muscle cells. In the cocultures, macrophages stimulated the proliferation of myoblasts. Myofibrils greatly enhanced the stimulating effect of macrophages, whereas lipopolysaccharide (LPS) completely abolished it. The culture medium conditioned by macrophages activated the proliferation of myoblasts that were incubated with myofibrils but inhibited it when myoblasts were incubated with LPS. Possibly, myofibrils and their constituent proteins activate macrophages in an alternative pathway, enriching the population with M2-type macrophages.Z.