Abstract: Peptidoglycan recognition proteins (PGRPs) are a class of pattern recognition receptors that are highly conserved from invertebrates to mammals. So far, PGRP is rarely reported in vertebrate species except for bony fish and mammals. This study constructed the eukaryotic expression plasmid of PGRP-S, a short peptidoglycan recognition protein in Chinese giant salamander, and explored its functins. Sequence analysis showed that the N-terminal of PGRP-S had no signal peptide, but had two closely spaced cysteine residues and two Zn²⁺ binding sites. Moreover, PGRP-S could be secreted to the exterior and also be retained within the cells. In vitro antibacterial experiments revealed that overexpression of PGRP-S significantly inhibited the proliferation of Edwardsiella tarda in HEK293T cells intracellularly and extracellularly. In addition, overexpression of PGRP-S enhanced NF-κB promoter activity and bound Lys-type and Dap-type peptidoglycan but without degradation ability.These results indicate that the Chinese giant salamander PGRP-S is functionally similar to mammalian PGRP-S.