Abstract： Objective To investigate the effects of mechanical ventilation with different pressure and duration on plasma IL-8 , IL-10 and lung ultrastructure in rats. Methods Thirty adult male SD rats weighting 200-220 g were randomly divided into 5 groups ( n=6 each ):control group ( group C ) , 2 h low airway pressure group (group L2, ventilated for 2 h at 15 cm H2O ) , 4 h low airway pressure group ( group L4, ventilated for 4 h at 15 cm H2O ) , 2 h high airway pressure group ( group H2, ventilated for 2 h at 25 cm H2O ) and 4 h high airway pressure group ( group H4 , ventilated for 4 h at 25 cm H2O).Mechanical ventilation was given at a rate of 40 tpm, at specified pressures for designed duration. The rats were sacrificed at 2 h or 4 h after ventilation. Blood samples were then collected and tested for levels of IL-8 and IL-10. Changes in lung ultrastructure was observed under light and electronic microscopes respectively. Results Compared with group C,the levels of IL-8 and IL-10 were significantly higher in groups L2, Lt, H2 and H4. Moreover, these levels appeared increasing along with longer duration of ventilation, with higher values in group L4 vs group L2 [IL-8: (71.5±7.6) ng/L vs (38.4±6.3) ng/L,IL-10:(364.5±18.6) ng/Lvs (271.6+21.3) ng/L, P<0.05], and in group H4 vs group H2 [IL-8: (140.7±23.5) ng/L vs (76.4±9.2) ng/L, IL-10: (472.8±22.5) ng/L vs (357.6±20.4) ng/L, P<0.05]. Over the same duration, levels of IL-8 and IL-10 were significantly greater with higher pressure used, namely, higher values in group H2 vs group L2, and in group H4 vs group L4 (P<0.05). Compared with group C, various degrees of inflammatory infiltration, emphysema, mitochondrial edema, dilated endoplama reticulum and expanded perinuclear space of lung ultrastructure existed in the other groups as shown by both light and electronic microscopes, which appeared to deteriorate along with longer ventilation time and higher pressure. Conclusions Higher pressure and longer duration for mechanical ventilation may induce IL-8 and IL-10, and also deteriorate lung tissue injury. Effective control of ventilation pressure and duration may ameliorate inflammation and injury of lung tissue.