The system of signaling pattern recognition receptors was studied in 8 cosmonauts aged 35 to 56 years before and after (R+) long-duration missions to the International space station. Peripheral blood samples were analyzed for the content of monocytes and granulocytes that express the signaling pattern recognition Toll- like (TLR) receptors localized as on cell surface (TLR1, TLR2, TLR4, TLR5, TLR6), so inside cells (TLR3, TLR8, TLR9). In parallel, serum concentrations of TLR2 (HSP60) and TLR4 ligands (HSP70, HMGB1) were measured. The results of investigations showed growth of HSP60, HSP70 and HMGB1 concentrations on R+1. In the;majority of cosmonauts increases in endogenous ligands were followed by growth in the number of both monocytes and granulocytes that express TLR2 1 TLR4. This consistency gives ground to assume that changes in the system of signaling pattern recognition receptors can stem .from the predominantly endogenous ligands' response to the effects of long-duration space flight on human organism.