Mannose receptor (MR) is a member of C-lectin family. It is mainly expressed on the surface of macrophage and immature dendritic cells. It has been shown that MR not only plays a significant role in innate immune responses, but also initiates acquired immune responses through processing and presenting antigens to activate T cells. In this study, we cloned and characterized pfMR of Chinese yellow catfish (Pelteobagrus fulvidraco). The expression profiles of pfMR mRNA in different tissues of P. fulvidraco were assessed by real-time quantitative reverse transcription PCR (qRT-PCR). To investigate the role of pfMR participating in the antibacterial infection, yellow catfish head kidney macrophages were infected with Edwardsiella ictaluri and competition binding test of mannan to MR was carried out. The phylogenetic tree analysis showed that MR of P. fulvidraco, Megalobrama amblycephala, Ctenopharyngodon idella, Danio rerio, and Oreochromis niloticus formed a clade. The mRNA of pfMR was expressed in all detected tissues with higher level in the kidney, spleen and muscle, and lowest expression in the blood. The expressions of pfMR, IL-1β and TNF-a mRNAs were all increased in cultured primary head-kidney macrophages after E. ictaluri infection. The infection of E. ictaluri also resulted in the over-expression of large number of superoxide anion (O₂^-·) and nitric oxide (NO) in the macrophages. The infection of E. ictaluri could significantly activate the production of O₂^-·at 30 min post treatment, while the amount of NO in the macrophage was significantly elevated at 12 h post treatment. Mannan significantly inhibited the engulfed GFP-E. ictaluri by macrophages through competition binding to MR. The engulfed GFP-E. ictaluri was significantly reduced by addition of EDTA, and restored by addition of Ca²⁺. The present study indicated that MR in head kidney macrophages of yellow catfish mediated phagocytosis of E. ictaluri and it was Ca²⁺-dependent.