Abstract: The present invention provides novel compositions for suppressing inflammation and for treating inflammatory disorders. These compositions contain at least one PARS-derived anti-inflammatory peptide or polypeptide and/or at least one PARI-derived anti-inflammatory peptide or polypeptide. The PARS- and/or PARI-derived peptides typically contain an amino acid sequence that mimics the respective N-terminal sequence of Activated Protein C-cleaved PARS or PARI, e.g., after activated protein C cleavage at residue Arg41 in human PARS and after residue Arg46 in human PARI. The invention also provides therapeutic methods of using the anti-inflammatory compositions described herein to suppress undesired inflammation and to treat inflammatory disorders. Additionally provided in the invention are methods of screening candidate compounds to identity novel anti-inflammatory agents.