In the present study ten isolates of Listonella anguillernm were isolated from Clarias guriepinus exhibited ulcerative lesions. The prevalence of infection was 16.7 %. The organisms were identified phenotypically to be a variant strains of L. anguillarum and the biochemical deviation were found in Voges Proskauer test and fermentation of mannitol. Experimentally, the infected fish showed severe skin ulcerations and high mortality rate. Electrophoresis of serum proteins revealed a significant decrease in α, β, and δ globulins on day 4 post infection (PI) and for β globulin only on day 8 PI. In addition, the total serum globulin was dropped significantly on day 4 PI and non-significantly on day 8 PI when compared with its value for control group. Moreover, the albumin / globulin ratio was significantly elevated in the inflected groups than in control one. The application of an indirect fluorescent antibody technique (IFAT) confirms the diagnosis of L. anguillarum and the results revealed presence of green yellowish fluorescent bacteria in the most stained tissue sections. A very strong immunofluorescence reaction was observed in spleen and kidneys while, the intestine showed reaction in its posterior portion only. In conclusion L. anguillarum considered as a causative agent of ulcerative syndrome in Cl.gariepinus and IFAT is a sensitive, rapid and specific test for diagnosis of L. anguillarum in fish.