A novel octahydroindolizine alkaloid, named dendrocrepidamine (1) with an unusual 18,19,19'-cyclopropanone-dendrocrepine skeleton, was isolated from the ethanol extract of the roots of Dendrobium crepidatum, along with six known compounds (2-7). The structure of 1 was elucidated through HR-ESIMS, NMR spectroscopic data and computational calculations. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells with IC(50) values in the range of 3.04-54.89 microM. In vivo, crepidatin (6) (80, 40 and 10 mg/kg) showed a significant protective effect against LPS-induced acute lung injury (ALI) in mice.