Abstract: To investigate the response of b2m gene from spotted sea bass (Lateolabrax maculatus) to bacterial and viral infections, we cloned the cDNA sequence of L. maculatus b2m gene by RACE-PCR. The full length of the cDNA was 1 383 bp with an open reading frame (ORF) of 357 bp encoding 118 amino acids. The similarity between deduced amino acid sequence of L. maculatus and the counterparts of other fishes was 44.8%−63.2%. The result of synteny analysis indicates that b2m loci were highly conserved in the fish genome. The b2m gene from L. maculatus was constitutively expressed in various tissues, with the highest expression level in spleen, and then gill, head kidney and brain. The mRNA expression level of b2m gene increased significantly in gill, head kidney and spleen after intraperitoneal injection of Lipopolysaccharide (LPS), Poly (I:C) and Edwardsiella tarda (Edw) by quantitative real-time PCR. These stimulants and pathogen can up-regulate the level of b2m gene of L. maculatus in various tissues, which indicates that b2m gene is involved in the immune defense process of anti-bacterial and anti-viral infection in L. maculatus.