Small ruminant producers sustain a considerable economic loss in many countries due to herd infection with Caseous lymphadenitis (CLA), a contagious chronic pyogenic disease of sheep and goat. This disease is caused by Corynebacterium pseudotuberculosis. In this study we investigated the prevalence of CLA in sheep and goat in Beni-Suef Governorate from the period of (March 2016 - April 2017) and examined the status of C. pseudotuberculosis drug resistance genes. Out of two hundred animals (165) sheep and (35) goat affected with external abscess, abscesses swabs were examined for presence of C. pseudotuberculosis. Prevalence of C. pseudotuberculosis was 13.9% in sheep and 8.6% in goat being mainly in the mandibular 56.3%, parotid 35.1% and prescapular 4.8%. Antibiotic sensitivity of the C. pseudotuberculosis showed its high susceptibility to quinolone, phenicol and sulpha and higher resistant to β-lactames, aminoglycosides and lincosamides. PCR amplification of the antibiotic resistance genes revealed the presence of β-lactames resistance gene (bla) in 40% of the isolates, aminoglycosides resistance gene (aadA2) in 42% of the isolates.The current study revealed the change of the C. pseudotuberculosis susceptibility to the antimicrobial effect than previous report. These results may necessitate the reconsideration of the general C. pseudotuberculosis management protocol based on the current situation which also seem to be specific for each locality depending on the previous exposure to antibiotic regimes for controlling C. pseudotuberculosis or other microorganism.