Mannose receptor (MR) is a pattern recognition receptor (PRR) that plays a significant role in immunity responses. Its role has been described extensively in mammals, but very rarely in fish. Recently, with the rapid development of an aquaculture industry cultivating large yellow croaker (Larimichthys crocea), infectious diseases caused by viruses, bacteria and parasites are becoming more frequent and more severe, in particular bacterial infections caused by Vibrio anguillarum, resulting in great economical losses. Extensive use of antibiotics as conventional treatment has led to microenvironment imbalances, development of drug-resistant bacteria and deposition of drug residues, which cause environmental pollution and ultimately affect human health. The purpose of this pilot study was to detect the transcriptional levels of C-type mannose receptor genes MRC1 (4710-bp ORF; encoding 1437 aa; a signal peptide, a SMART RICIN domain, a SMART FN2 domain, eight SMART CLECT domain, and a transmembrane helix region) and MRC2 (3996-bp ORF; encoding 1484 aa; a SMART FN2 domain, eight SMART CLECT domains, and a transmembrane region) in the liver, kidney and spleen tissues of L. crocea challenged by V. anguillarum, to explore the effective domain and the molecular response mechanisms of MRC1 and MRC2, and, ultimately, to explore the possibility of developing a vaccine targeting V. anguillarum infections.