Abstract: Mastitis continues to be a major economic issue for dairy producers all over the world. Staphylococcus aureus is frequently isolated from bubaline mastitis and brings about glandular tissues changes obliterating the milk producing cells. Elimination of this organism from dairy herds requires treatment of infected mammary glands with antimicrobial agents and aggressive culling of refractory animals. The present study was designed to evaluate the disease characteristics of Staphylococcus aureus mastitis in buffaloes and antibiotic susceptibility profiles of isolates. Visual inspection and palpation indicated as; asymmetry between hind quarters (n = 3), symmetry between hind quarters (n = 3), asymmetry between front quarters (n = 1), symmetry between front quarters (n = 5), Clinical symptoms (n = 2), udder and teat’s wounds (n = 2), scar tissue (n = 1), warts (teat) (n = 1) and all others parameters were normal. A total of 100 milk samples (20 clinical and 80 sub-clinical) from mastitic quarters of buffaloes were collected. The antibiotic susceptibility profiles of recovered isolates Staphylococcus aureus were as; co-trimaxazole (100%), oxytetracycline (95.65%), amoxicillin (86.95%), gentamycin (86.95%), ampicillin (82.60%), ciprofloxacin (82.60%), chloramphenicol (82.60%), enrofloxacin (69.56%) and novabiocin (60.86%).