It is known, that stress and inflammation lead to disorders in rats mesenteric microcirculatory system. These disorders are connected with mast cells (MC) activation. Activation of MC by compound 48/80 also led to microcirculatory system disorders. MC stabilization by ketotifen decreased them. Proline containing peptides (PGP, PG, GP) had a protective effect in microcirculatory dysfunction under conditions of inflammation and stress. Mechanism of peptides protective action is not clear. This action can be connected with MC activation and may be direct as well as indirect. The effect of PGP on rats isolated peritoneal mast cells activity (secretion of enzyme b-hexosaminidase, %) in vitro was investigated. We used two different MC activators – synacten (ACTH1-24, Novartis) and compound 48/80 (Sigma). Synacten (2·10^-5 M) increased MC secretion of b-hexosaminidase (norm. 19.311.32, syn. 25.041.04), and MC incubation with PGP (6·10^-5 M) prevented it (21.810.93). Compound 48/80 also increased b-hexosaminidase secretion (50.323.1). But PGP didn't prevent MC activation by compound 48/80 (46.86.62). It is possible that effect of PGP on mast cells activity depends on the way of their activation.