Objective To study the effect of low tidal volume ventilation in patients with respiratory failure due to neuromuscular disease. Methods Fifty-seven patients with neuromuscular disease and respiratory failure requiring mechanical ventilation were divided into low tidal volume ventilation group ( group A: 2 7 cases ) and routine tidal volume ventilation group (group B: 30 cases ). Indices of airway pressure and blood gas were recorded. The levels of TNF, IL-6, IL-8 in Bronchoalveolar Lavage Fluid (BALF) were measured after ventilation. The survival rates of 14 days and weaning success rates of 14 days were observed. Results The pH value in arterial blood gas at 0.5 and 24 hour after ventilation was 7.30 ± 0.08,7.40 ± 0.06 in group A,which were significantly lower than those of 7. 39 ± 0. 06,7.47 ± 0. 04 in group B at the same time point ( P ＜ 0. 05 ). The PaCO2 levels at0.5 and24 h were (60.4 ± 16.9)mm Hg and (38.2 ±7.3)mm Hg in group A,which were also significantly higher than those of (46. 6 ±8. 1 )mm Hg and (29.2 ±6.9)mm Hg at the same time point in group B (P ＜ 0.05 ). The airway peak pressure at 0.5 and 24 hour were (21.5 ± 4.5 ) mm Hg and ( 18.6 ± 3.8 ) cm H2O in group A,which were significantly lower than those of (29.4 ±5.1)cm H2O and (31.3 ±4.7)cm H2O at the same time point in group B (P ＜ 0. 05 ). The levels of TNF in BALF at 24 and 48 hour were ( 1385 ± 341 ) ng/L and (1345 ±411 )ng/L in group A,which were significantly lower than those of (1914 ± 501 )ng/L and (2214 ± 544)ng/L in group B at the same time point (P ＜0.01 ). The level of IL-6 in BALF at 24 and 48 hour were (249 ±64)ng/L and (209±49)ng/L in group A,which were significantly lower than those of (324 ±79) ng/L and (343 ±60)ng/L in group B at the same time point ( P ＜ 0. 01 ). The levels of IL-8 in BALF at 24 and 48 hour were (79. 4 ±23.6) ng/L and (92. 7 ± 32. 5)ng/L in group A,which were significantly lower than those of (143 ± 36)ng/L and (162 ±49)ng/L in group B at the same time point (P ＜0.01 ). No significant difference was found in the survival rates of these two groups (100% vs. 96. 7% ,P ＞0. 05). The higher weaning success rate was observed higher in group A (59. 3% ) than group B (33.3%, P ＜ 0. 05 ). Conclusions For patients with respiratory failure resulting from neuromuscular disease,low tidal volume ventilation can decrease ventilation-induced cytokine release, alleviate ventilator-induced lung injury, and increase the success rate of ventilator weaning.