As oedematous skin disease (OSD) became an endemic disease in buffaloes in Egypt. This study was carried out on 75 buffaloes from a private farms at Sohag Governorate to determine occurence, clinical finding, age and sex susceptibility, ELISA, molecular diagnosis and antibiogram of Corynebacterium pseudotuberculosis. Bacteriological examination of the samples revealed that 44 cases (58.7%) were positive, 30 cases of them (68.2%) were in form of the closed lesions and 14 (31.8%) were open lesions. The main clinical signs of the infected buffaloes had been described. Isolated bacteria were subjected for morphological and biochemical identification. The results obtained revealed that 38 isolates (86.4%) were Corynebacterium pseudotuberculosis in single infection and mixed infection with both Staph. aureus 3 isolates (6.8%) and strept. Pyogens 3 isolates (6.8%). Pathogenicity test for C.pseudotuberculosis in guinea pigs indicated that all isolates were pathogenic and cause death of inoculated animals. The OD of ELISA above the cutoff point (0.25) was recorded in serum samples. PCR identification of Pld gene revealedpositive isolates. Results of antibiograms indicated that most of isolates were highly sensitive to Rifampicin, Ciprofloxacin, Enrofloxacin, Gentamycin, Penicillin and streptomycin. Treatment by effective antibiotics, antihistaminic and eradication of the flies achieved the recovery from the disease.