Abstract： Objective To investigate the effects of acute hypervolemic hemodilution (AHH) with hydroxyethyl starch (HES) 130/0.4 on the lung in a rabbit model of sepsis and their possible mechanism. Methods Thirty healthy New Zealand rabbits were randomly divided into three groups (n=10 each): group sham operation (C), group sepsis model (E) and group AHH. Sepsis model was reproduced with modified colon ascendens stent peritonitis (CASP). In group C laparotomy was done but without puncturing the colon. At 4 hours after CASP, AHH was carried out intravenous infusion of 6% HES 130/0.4 20 ml/kg at 20 ml/min. Lactated Ringer solution was infused at 10 ml·kg-1·h-1 in all three groups during the experiment. The animals breathed spontaneously during the experiment. A catheter was introduced into the right carotid artery for blood sampling, and it was connected to a pressure transducer for continuous mean arterial pressure (MAP) and heart rate (HR) monitoring. At 4 hours and 8 hours after CASP, a median abdominal incision was made and photographic documentation of abdominal situs was made. At the same time arterial blood samples were drawn at 4 hours and 8 hours after CASP for blood gas analysis and determination of hemoglobin (Hb) and hematocrit (Hct). The plasma component was separated and tumor necrosis factor-α (TNF-α) was measured. Respiratory rate and urinary output were record. The rabbits were sacrificed at 8 hours after CASP. The right lungs were immediately removed for determination of total protein concentration in broncho-alveolar lavage fluid (BALF). The wet/dry (W/D) lung weight rate were calculated. The sections of lung were stained with hematoxylin and eosin for light microscopic examination and the injury score was recorded. Results ①MAP declined gradually and HR tended to accelerate during the course of the experiment in group E, but no significant differences were found in both group C and group AHH. ②After AHH, the Hb and Hct decreased by 20% in group AHH. In group E, arterial oxygen saturation (SaO2), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2) and pH decreased significantly at 8 hours after CASP compared with group C (all P<0.05). ③TNF-α concentration in plasma was higher in group E and group AHH than in group C at 4 hours after CASP (both P<0.05). At 8 hours TNF-α concentration was increased in group E compared with group C (P<0.05), but there was no significant difference between group C and group AHH. ④In group E, score of morphological changes in lung was significantly increased compared with group AHH (6.9±1.4 vs. 11.2±1.7, P<0.05). Conclusion AHH with HES 130/0.4 can protect the lungs from sepsis. Inhibition of proinflammatory cytokines may be involved in the mechanism.