Background Nitric oxide (NO) plays an important role in acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and in ventilator-induced lung injury (VILI). A change in the balance of endothelin-1 (ET-1) and NO in the ALI/ARDS can also add to these problems. However, the profile of ET-1 and the balance of ET-1 and NO are still unknown in a VILI model.Methods Models of oleic acid induced ALI were established in dogs; these models were then randomized into three groups undergone different tidal volume (VT) mechanical ventilation, which included a VT6 group (VT equaled to 6 ml/kg body weight, positive end expiratory pressure (PEEP) equaled to 10 cmH_2O, n=6), a VT10 group (VT equaled to 10 ml/kg body weight, PEEP equaled to 10 cmH_2O, n=4) and a VT20 group (VT equaled to 20 ml/kg body weight, PEEP equaled to 10 cmH_2O, n=6) for 6-hour ventilation. The levels of ET-1 and NO in serum and tissue homogenates of lung were observed throughout the trial.Results PaO_2 was increased after mechanical ventilation, but hypercapnia occurred in the VT6 group. The magnitudes of lung injury in the VT20 group were more severe than those in the VT6 group and the VT10 group. Serum levels of ET-1 and NO increased after ALI models were established and slightly decreased after a 6-hour ventilation in both the VT6 group and the VT20 group. The serum ET-1 level in the VT20 group was higher than that in the VT6 group and the VT10 group after the 6-hour ventilation (P <0.05) while the serum NO levels were similar in the three groups (all P >0.05). There was no significant difference in serum ratio of ET-1/NO between any two out of three groups (P >0.05), although there was a significant positive relationship between serum ET-1 and serum NO (r=0.80, P<0.01). The levels of ET-1 and NO in the lung were increased after ventilation. The lung ET-1 level in the VT20 group was significantly higher than that in the VT6 group and VT10 group (both P<0.05) while there was no significant difference in lung NO levels between two groups (P>0.05). In the lung tissue, the ratio of ET-1/NO was significantly higher in the VT20 group than in the VT6 group and VT10 group after the 6-hour ventilation (P<0.05) as there was a significant positive relationship between ET-1 and NO in the lung (r=0.54, P<0.05).Conclusions The production of ET-1 and NO was increased in serum and lung tissue in a VILI model. But the ET-1 levels increased much more than the NO levels in the lung, though there was a significant positive relationship between levels of ET-1 and NO. These results showed that there was an interaction between ET-1 and NO in a VILI model and changing the balance of ET-1 and NO levels might contribute to the pathophysiologic process of VILI.