CD81, also known as the target of an antiproliferative antibody 1 (TAPA-1) in human, is a member of tetraspanin integral membrane protein family. This protein plays many important roles in immune and other physiological functions. In this report, we characterized and analyzed expression of the channel catfish CD81 transcript. The full-length of channel catfish CD81 cDNA comprised of 1130 nucleotides, including an open reading frame which appears to encode a putative peptide of 234 amino acid residues. By comparison with the human counterpart, the channel catfish CD81 peptide could be divided into domains, including four transmembrane domains, three intracellular domains, and one of each small and large extracellular loops. The degree of conservation of the channel catfish CD81 amino acid sequence to that of mammalian counterparts ranged from 65% to 67%. The large extracellular domain shows the least conservation between fish and mammals. However, the characteristic Cys(159)-Cys(160)-Gly(161) motif and Cys(176/188) in this domain were conserved. The channel catfish CD81 transcript was detected by RT-PCR in spleen, head kidney, liver, intestine, skin and gill. This result provides important information for further elucidating CD81 functions in channel catfish.