This study was conducted to determine the effectiveness of rapid IV administration of hypertonic saline solution (HSS) for resuscitating buffaloes suffering from diarrhea. Twenty diarrheic buffaloes were selected from the field and randomly divided into two equal groups viz group A and B. Buffaloes of group A were treated with normal saline (NS; 0.9%NaCl) solution @ 32 ml/kg BW, while group B was infused with hypertonic saline solution (HSS; 7.5% NaCl) @4 ml/kg BW, followed by normal saline solution @ 10 ml/kg BW. Buffaloes were then monitored for 48 hours after initiation of fluid replacement. Diarrhea had profound effects on the partial pressure of O2 and increased pressure of CO2, mean arterial pressure (MAP), relative plasma volume (rPV) and blood pH. Infusion of HSS in buffaloes caused significant increase in MAP (74  2 to 100  5), plasma volume, systemic O2 delivery and blood pH (7.12  0.03 to 7.41  0.05) in comparison to NS. Significant reduction in PaCO2 (39 ± 2 to 28 ± 1 mm Hg) was also observed in group B. It was concluded from the study that hypertonic saline solution has beneficial effects in resuscitating the animals fromhypovolemia and acidemia caused by diarrhea.