This report was delineated to study the clinical, bacteriological and therapeutic aspects concerned with acute coliform mastitis in buffaloes. Bacteriological examination of 80 quarter milk samples obtained aseptically from 56 buffaloes with acute mastitis revealed that coliform bacteria was the most common pathogen (45 cases) followed by Staphylococcus aureus (seven cases) then Streptococcus uberis (three cases), and Streptococcus agalactiae (one case). Clinically, hotness, swelling and painful reaction with serous excretion containing clots was recorded in buffaloes with coliform mastitis. The efficacy of ceftiofur was evaluated in the treatment of buffaloes with acute coliform mastitis. Parenteral ceftiofur neither improved clinical signs nor returned milk to pre-infection production level, whereas intramammary ceftiofur and combination of intramammary with parenteral ceftiofur improved the clinical signs in 10/15 and 12/15 buffaloes, respectively. On quarter level, 3/17, 12/17 and 15/21 quarters recovered in groups received parenteral, intramammary and combination therapy, respectively. This study demonstrates that systemic ceftofur is not effective in the treatment of clinical coliform mastitis in buffaloes.