Objective To evaluate the effect of silent information regulator 1 (sirt1) on inflammatory response to ventilation‑associated lung injury (VILI) in mice. Methods A total of 40 SPF healthy male C57BL/6N mice, aged 8 weeks and weighing 20‒25 g, were used. According to the random number table method, they were divided into four groups (n=10): a sham operation group (group S), where mice were intubated without mechanical ventilation; an VILI group (group M), where mice were mechanically ventilated after intubation; a sirt1 knockdown group (group si‑sirt1), where mice were transfected with sirt1 small interference RNA; and a sirt1 knockdown and VILI group (group si‑sirt1+M), where mice were transfected from sirt1 small interference RNA before mechanical ventilation. Mechanical ventilation parameters were listed as follows: ventilation frequency 60 bpm, tidal volume 28 ml/kg, the fraction of inspiratory oxygen 21%, inspiratory/expiratory ratio 1∶2, and ventilation time 4 h. After mechanical ventilation, the mice were sacrificed to collect lung tissue and bronchoalveolar lavage fluid (BALF). The concentrations of interleukin (IL)‑1β and IL‑6 in BALF were determined by enzyme‑linked immunosorbent assay (ELISA). The pathological results were observed by hematoxylin‑eosin (H‑E) staining. The ratio of wet/dry (W/D) weight was calculated, while the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissues were determined by ELISA. The levels of sirt1, p120, and occludin in lung tissues were detected by Western blot. Results Compared with group S, group M, group si‑sirt1, and group si‑sirt1+M showed significant injury in lung tissues, and increases in W/D ratio, and IL‑1β, and IL‑6 concentrations (P<0.05), down‑regulated expression of sirt1, p120 and occludin (P<0.05), increased MDA level in lung tissue (P<0.05), and decreased SOD level (P<0.05). Compared with group M, group si‑sirt1+M showed more severe lung tissue injury, increases in W/D ratio, and IL‑1β, and IL‑6 concentrations (P<0.05), down‑regulated expression of sirt1, p120 and occludin (P<0.05), increased MDA level in lung tissue (P<0.05), and decreased SOD level (P<0.05). Conclusions Low expression of sirt1 in mice causes aggravated inflammation in lung tissue caused by mechanical ventilation.