The present study attempted to understand the histopathological index of striped catfish (Pangasianodon hypophthalmus) in challenge with Edwardsiella ictaluri, the causative agent of bacillary necrosis of Pangasius. Total of 355 healthy striped catfish juveniles was challenged with E. ictaluri (25 control; 330 infected). After the challenge, a total of 355 samples of the trunk kidney, liver, and spleen were collected at five different time points including just prior to infection, 24, 48, 264 and 312 hours post-infection (hpi) to measure the represented tissue damage of the fish. Results showed that many areas of the diseased liver, kidney, and fish organ tissues have been congested and hemorrhaged early at 24 hpi. The number of macrophage centers in the kidney and spleen increased at 24 - 48 hpi. Tissue damage (multifocal hemorrhages; necrosis) increased sharply from the period 48 - 256 hpi. The increased number of dead fish throughout infection, particularly the period from 48 to 200 hpi. At 312 hpi, the histopathological index was the highest, so the mortality rate was the highest during the experimental period.