OBJECTIVE To investigate the value of venous pressure gradient [D(c-i)VP] between central venous pressure (CVP) and iliac vein pressure (IVP) in assessing the responsiveness to volume resuscitation in hypovolemic patient undergoing mechanical ventilation. METHODS Thirty hypovolemic patients undergoing mechanical ventilation, with maintenance of similar ventilation conditions, graded volume loading was performed with 250 ml Ringer lactate solution (LR) for each infusion in hypovolemic patients, until mean arterial pressure (MAP) ≥65 mm Hg(1 mm Hg = 0.133 kPa), CVP≥8 mm Hg, strong pulse, perfusion improvement (recovery in the end) were reached. Before infusion, 10 minutes after infusion, and at the end of recovery, the heart rate (HR), MAP, CVP, IVP, stroke volume (SV), thoracic fluid content (TFC) and D(c-i)VP were measured and recorded, the correlations between D(c-i)VP and TFC, SV before and after infusion were analyzed. RESULTS Before infusion, 10 minutes after infusion, and at the end of recovery, no significant difference was found in HR, MAP, CVP, and IVP,while D(c-i)VP (mm Hg) was obviously lowered (4.89 ± 1.70, 2.80 ± 1.44, 2.10 ± 1.30, respectively), and SV (ml) and TFC (ml) were significantly increased (SV was 42.0 ± 10.5, 49.0 ± 8.3, 58.0 ± 12.1, respectively; TFC was 30.0 ± 9.6, 38.0 ± 8.6, 43.0 ± 11.1, respectively), with statistical differences (P < 0.05 or P < 0.01). Negative correlations were found between D(c-i)VP and TFC, SV [r(1)=-0.580, P(1)=0.004; r(2)=-0.462, P(2) =0.017]. CONCLUSIONS In the course of fluid resuscitation in hypovolemic patients undergoing mechanical ventilation, the D(c-i)VP was significantly reduced with fluid resuscitation. At the same time, significant correlations between D(c-i)VP, TFC and SV were demonstrated. The measurement of D(c-i)VP could help guide fluid resuscitation in hypovolemic patients undergoing mechanical ventilation.