| Grass carp reovirus (GCRV) is one of the main pathogens that causes severe grass carp hemorrhagic disease. GCRV type II (GCRV-II) is currently prevalent strain in China. At present, the difference between the clinicopathological symptoms and virus distribution of naturally and artificially injection infected Ctenopharyngodon idella with GCRV-II virus is still unclear. In this study, we compared the clinical symptoms of naturally diseased and artificially injected Ctenopharyngodon idella, and found that the eye socket, operculum, mouth cavity, abdomen, fin base, intestine and muscle of the diseased grass carp showed obvious punctate hemorrhage. The bleeding of the latter was more serious than that of the former. Comparing histopathological sections, it was found that the infected tissues had different degrees of congestion and erythrocytes accumulation. Among them, the intestines, muscles and hepatopancreas of the artificial injection of Ctenopharyngodon idella were more severely affected, showing more serious intra-tissue bleeding and lesions. The gills and spleen of naturally diseased Ctenopharyngodon idella are more severely affected, the gills show more serious hyperaemia and inflammatory hyperplasia, and large areas of hemosiderin agglutination lesions in the spleen. qRT-PCR and Western blot tests showed that GCRV is distributed in different tissues. The head kidney has the relatively high viral load in diseased fish of the two infection methods. The viral load of the hepatopancreas, intestine and muscle is higher in artificially infected fish. The amount of virus is higher in the trunk kidney, gill and spleen in naturally diseased fish. Therefore, the hepatopancreas, intestine and muscle may be the main target organs of GCRV invasion in artificial infection, while the gill may be the main target organ of GCRV invasion in the case of natural disease, and the target organ for virus accumulation is the head kidney. The head kidney is the "virus library" of GCRV. This study is helpful to deeply analyze the pathogenesis of GCRV and the immune responses of grass carp, and also provides references for the prevention and treatment of grass carp haemorrhagic disease and the development of vaccine.