To better understand the pathogenesis of the Ostreid Herpesvirus-1 (OsHV-1) to blood clam, experimental infection was conducted by injecting filtered tissue homogenate into the gastropod of each calm. Experimental clams were randomly allocated into 3 groups: blank control group, negative contral group, OsHV-1 infected group. After the experiment, the temporal distribution patterns of OsHV-1 infection loads in six different tissues were assayed with quantitative PCR (qPCR). No virus was detected in clams injected with sea water and the negative control tissue homogenate. While virus DNA were detected in animals injected with tissue homogenate prepared from naturally infected clams. The virus DNA loads in tissues fluctuated first, and then reached about 106 copies viral DNA per ng of total DNA. Pathological changes including lysed connective tissue, dilation of the digestive tubules, eosinophilic inclusion bodies, nuclear chromatin margination and pyknosis were found in affected animals. Transmission electron microscopy (TEM) revealed herpes-like viral particles within the connective tissue of the mantle. These viral particles were about 90-110 nm in diameter with an electron-dense nucleoid packaged in capsid, which resembled those found in naturally infected clams. Overall, this work demonstrated the pathogenesis of OsHV-1 to blood clams and closely associated with the mass mortality of them. Additionally, our work also indicated the stress reaction after injecting OsHV-1 might play a role in the suppression of OsHV-1 replication, while the mechanisms need to be further studied.