Objective To investigate the effects and mechanism of short chain fatty acids (SCFAs) on lipopolysaccharide(LPS) induced acute respiratory distress syndrome (ARDS) in rats. Methods Twenty male SD rats were randomly divided into control group, model group, low-dose SCFAs group and high-dose SCFAs group (5 each). Rats in control and model groups were given normal saline, in low-dose SCFAs group were given sodium acetate 300 mg/kg, sodium propionate 100 mg/kg and sodium butyrate 100 mg/kg, and in high-dose SCFAs were given sodium acetate 600 mg/kg, sodium propionate 200 mg/kg and sodium butyrate 200 mg/kg by gavage for 7 days in advance. And then the rats in control group were perfused with normal saline, and in the other 3 groups were perfused with LPS (5 mg/kg) into trachea to establish ARDS model. The rats were sacrificed 12 hours after modeling, and the arterial oxygen partial pressure (PaO₂) and lung wet/dry weight ratio (W/D) were measured, and HE staining was performed to observe the pathological changes of lung tissues. The concentrations of tumour necrosis factor (TNF)-α, interleukin(IL)-6 and IL-10 in serum and bronchoalveolar lavage fluid (BALF) were detected by ELISA. Western blotting was used to detect c-Jun N-terminal kinase (JNK), p-JNK, extracellular regulated protein kinases (ERK), p-ERK, p38 mitogen-activated protein kinase(MAPK), p-p38 MAPK, nuclear factor kappa-B (NF-κB) p65 and p-NF-κB p65 protein expression in lung tissues. The expression of tight junction protein ZO-1 and Occludin in colonic tissue were detected by immunohistochemistry. Results Compared with control group, PaO₂ decreased, lung W/D and lung pathological injury score increased, the concentration of TNF-α and IL-6 in serum and BALF significantly increased, and the concentration of IL-10 increased, the relative protein expressions of p-JNK/JNK,p-ERK/ERK, p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in lung tissues significantly increased, while the relative expression of ZO-1 and Occludin protein significantly decreased in colonic tissues in model group (P<0.05). Compared with model group, PaO₂ increased, lung W/D and lung pathological injury score decreased, and TNF-α, IL-6 in serum and BALF decreased,the concentration of IL-10 increased further, while the relative expressions of p-JNK/JNK, p-ERK/ERK, p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 protein in lung tissue decreased, and the relative expression of tight junction protein ZO-1 and Occludin in colon tissue increased in low and high dose SCFAs groups (P<0.05). Compared with low-dose SCFAs group, the indexes mentioned above in the high-dose SCFAs group improved more significantly (P<0.05). Conclusion SCFAs could regulate immunity and inflammation, and effectively improved LPS-induced ARDS in rats, the mechanism might be related to enhancement of intestinal barrier and inhibition of MAPK and NF-κB signaling pathway activation, thereby reducing the release of inflammatory factors and increasing the production of anti-inflammatory factors.