Abstract: Human liver-expressed antimicrobial peptide 2（LEAP-2） as a novel active peptide exhibits antimicrobial activities and regulates body weight. To understand the basic information of human LEAP-2, in this study, we utilized online biological software and tools for systematic bioinformatics analysis. The analysis of the primary structure showed that human LEAP-2 had 77 amino acid residues, consisting of 18 kinds of amino acids. Molecular weight was 8.81 kDa, and theoretical pI was 10.31. Human LEAP-2 presented an instable hydrophilic protein, composed of signal peptide, propeptide and mature peptide. There were 4 glycosylation sites and 7 phosphorylation sites. The main secondary structural elements were α-helix and random coil. Three-dimensional structure of the mature peptide was composed of hydrophobic flexible N terminus, rigid central core and flexible C terminus, stabilized by the two disulfide bonds. The results of multiple sequence alignment of LEAP-2 from different species revealed that the sequences of signal peptide and propeptide had a certain difference, while the mature peptide sequences displayed high similarity and kept highly conserved region during long evolutionary process. The analysis of phylogenetic tree suggested that molecular evolution process of LEAP-2 in different species was basically consistent with phylogenetic relationship of species. The research results provide a theoretical basis for further in-depth study of the biological function and molecular mechanism of LEAP-2.