Infectious hematopoietic necrosis virus (IHNV) is one of the most important fish viral pathogens causing acute, systemic and often virulent disease in culture rainbow trout. In this study, we have investigated the infection mechanisms of high and low pathogenic IHNV in rainbow trout by RNA seq-based transcriptome analysis. Healthy rainbow trout were infected with two types of IHNV at 20°C and RNA was extracted from kidney and spleen of juvenile fish to analyze transcriptome at 1, 3, and 5days post-infection. After mapping the RNA sequences to each genome, DEG analysis and KEGG pathway analysis were performed. When IHNV were delivered by intraperitoneal injection (9.8×105 PFU/fish), the mortality caused by IHNV-Shizuoka ware 45~70% while IHNV-Nagano were 10~60%. In addition, FoxO signaling and NOD-like pathway had increased in IHNV-Shizuoka infected fish than IHNV-Nagano infected group in KEGG pathway. Also, RT-PCR was used to assess viral load and gene expression of selected immune genes. Analyses of in vivo replication showed that P and L gene of IHNV-Shizuoka are constantly more prevalent than M, U and G gene in rainbow trout injected with 1× 104 PFU/fish for each IHNV genotypes. In analyses of the host immune response, IHNV-Nagano-infected fish showed higher expression of innate immune-related genes such as IFNg, IL 1b while IHNV-IHNV-Shizuoka-infected fish showed higher expression of TNF-α gene.