Abstract： Objective To evaluate the effect of 7. 5% hypertonic saline(HS)and 6% hydroxyethyl starch (HES)130/0.4 on early fluid resuscitation for severe sepsis. Methods Prospective randomized control trial was carried out in intensive care unit(ICU)of the Affiliated Hospital of Jianghan University. One hundred and thirty-five patients with severe sepsis were randomly divided into three groups, each group consisted of 45 patients. Patients in HS+HES group received lactated Ringer solution following 4 ml/kg of 7. 5%HS and 6%HES 130/0. 4 500 ml, those in HES group received lactated Ringer solution following 6%HES 130/0.4500 ml, and those in the lactated Ringer group(RL group)received lactated Ringer solution only. Mean arterial pressure(MAP), oxygenation index(PaO2/FiO2), arterial lactate(Lac), lactate clearance rate,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score, fluid infusion volume, urine output as well as incidence of multiple organ dysfunction syndrome(MODS), and mortality were compared among three groups at 6 hours and 24 hours after ICU admission. Results At 6 hours after ICU admission, MAP [mm Hg(1 mm Hg=0. 133 kPa): 68. 7±3. 0], PaO2/FiO2(mm Hg: 262.2±17.4), lactate clearance rate [(21±4)%]in HS+HES group were significantly higher than those in HES group[MAP: 63. 8±3.5,PaO2/FiO2: 252.0 ± 21.2, lactate clearance rate:(11± 2)%]and RL group[MAP: 62.6 ± 3. 6, PaO2/FiO2 :248. 4±17.0, lactate clearance rate:(9± 1)%, all P＜0. 01]. Arterial Lac in HS+HES group(mmol/L:3. 5±0. 7)was significantly lower than that in HES group(4. 1±0. 7)and RL group(4. 0±0. 7, both P＜0. 01). There was no significant difference in APACHE Ⅱ score between HS+HES group(13. 2±1.9)and HES group(14.0±1.6), and the APACHE Ⅱ score in HS+HES group was significantly lower than that in RL group(15. 2 ± 1.7, P＜ 0. 01). At 24 hours after ICU admission, PaO2/FiO2(mm Hg: 303.3 ± 17.3)was significantly higher in HS+HES group than that in HES group(282.9 ± 21.1)and RL group(268. 9 ±15.2,both P＜ 0.01). There was no significant difference in MAP, arterial Lac, lactate clearance rate and APACHE Ⅱ score among three groups. At 6 hours and 24 hours after ICU admission, fluid infusion volume in HS+HES group(ml, 6 hours: 1 877. 8±215. 2, 24 hours: 5 475.6±208.8)was markedly less than that in HES group(6 hours: 2 505.6±276.2, 24 hours: 6 383. 3±287.4)and RL group(6 hours: 3 496. 7±325.5, 24 hours: 7 439.6±229.6), yet urine output in HS+HES group(ml, 6 hours: 294.2±36.9,24 hours: 2 793.8 ±37.1)was significantly higher than that in HES group(6 hours: 248.9 ± 25. 3,24 hours: 2 248. 9±25. 3)and RL group(6 hours: 178. 9±14.8, 24 hours: 2 000. 4±147.0, all P＜0. 01).The incidence of MODS in HS+HES group(6.7%)was statistically lower than that in RL group(28. 9%,P＜0. 05), while no obvious difference was found between HS+HES group and HES group(17.8%, P＞0. 05). There was no significant difference in mortality among three groups(HS+HES group: 2.2%, HES group: 4.4%, RL group: 8.9%, all P＞0. 05). Conclusion 7.5%HS and 6%HES 130/0. 4 could improve the effect of early fluid resuscitation on severe sepsis, and it could lower the incidence of MODS.