Abstract: AIM:To observe the role of salidroside (SDS) in the treatment of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and to further explore the underlying mechanism by which salidroside exerts protective effects on LPS-induced ALI. METHODS: Sprague Dawley rats were divided randomly into three groups: normal saline (NS) control group, LPS group and LPS+SDS group. The animal model of ALI was established by intratracheal administration of LPS ［0.5 mg/(ml·kg)］ and microinjection pump was used to inject solution through the right external jugular vein. NS was injected in NS group and LPS group for 4 h. In LPS+SDS group, LPS was instilled intratracheally and after 0.5 h, liquid SDS ［5 mg/(ml·kg)］ was injected for 4 h. After 4.5 h, histological changes of the lungs were observed, and the left lung wet-to-dry (W/D) weight ratios and the protein content in BALF were evaluated. Meanwhile, TNF-α, IL-6, IL-10, LDH and MPO in lung homogenate were measured. RESULTS: Histological study showed congestion, edema and sequestration of inflammatory cells in the lung tissues in LPS group, but the lung injury was significantly alleviated in LPS+SDS group. W/D ratio, protein content in BALF, and contents of TNF-α, IL-6, IL-10, LDH and MPO were significantly increased in LPS group (P<0.05). SDS treatment inhibited all these increased parameters (P<0.05) and increased the content of IL-10 (P<0.05). CONCLUSION: Salidroside plays an important role in treatment of LPS-induced ALI. Its protective mechanism is correlated with the inhibition of mediators of inflammation.