ABSTRACTMandarin fish ranavirus (MRV) is widely spread in China and causes huge economic losses to the mandarin fish (Siniperca chuatsi) aquaculture. However, the pathogenesis of MRV is still unclear. In the present study, mandarin fish were artificially infected with MRV, and then different gut compartments from diseased fish were subjected to histologic analysis by H&E staining, quantification of proinflammatory genes and MRV copies by qPCR. MRV‐MCP protein expression was assessed using indirect fluorescence assay (IFA) and immunohistochemistry. Proliferation of IgM+ B cells was evaluated by indirect fluorescence assay (IFA). Then, we found that MRV infection caused serious histologic lesions along with inflammatory cell infiltration, especially in the foregut. A significant accumulation of IgM+ B cells was detected in the foregut (~6.5‐fold) and hindgut (~3.3‐fold), respectively. The expression of inflammation‐related genes such as IL‐1β, IL‐6, IL‐8, TNF‐α, CSF1r and NCF1 was significantly upregulated in the foregut, varying from ~2.8‐fold to ~11.9‐fold. In addition, MRV exhibited foregut tropism, according to the investigation of viral loads and MCP protein expression. Overall, our findings indicated that MRV‐induced hyperinflammation in the gut eventually led to enteritis. This study provided new insights into uncovering the pathogenesis of MRV infection.