In this study, α2M gene from Hyriopsis cumingii was cloned. The accession number in the Genbank is DQ993157.1.The full-length cDNA spans 5124bp, which contains an open reading frame of 4836bp, 5’ untranslated region of 35bp and 3’untranslated region of 253bp. The open reading frame encodes a protein of 1611 amino acids. The first 23 amino acids in the N-terminus is recognized as a signal peptide. The relative molecular weight of the deduced protein is 177571.8D, isoelectric point is 5.49, and instability index is 39.53, which is classified as stable. Furthermore, Expression of α2M in different tissues of Hyriopsis cumingii was determined by RT-PCR and the result showed no expression was detected in mantel, conductor muscle, intestine, sexual gland except hemocyte. After injecting by Escherichia coli and Aeromonas hydrophila, α2M expression level had a certain amount of rise 12h later, which fully proved the existence of α2M immune system in Hyriopsis cumingii.