Summary: Excessive activation of macrophages is implicated in various inflammatory injuries. Salidroside (Sal), one of the main bioactive components ofRhodiola Sachalinensis, has been reported to possess anti-inflammatory activities. This study aimed to examine the effect of Sal on the activa- tion of macrophages and the possible mechanism. The lipopolysaccharide (LPS)-stimulated phrobol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage models were established. The changes in the inflammatory profiles of THP-l-derived macrophages were determined. The results showed that Sal significantly decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), interleukin-lbeta (IL-1β), interleukin-6 (IL-6) and tumor necrosis fac- tor-or (TNF-a) at both mRNA and protein levels in THP-l-derived macrophages, and the effect was dose-depedent. Moreover, NF-B activation was significantly suppressed and the phosphorylation of ERK, p38 and JNK was substantially down-regulated after Sal treatment. The findings suggested that Sal can suppress the activation of LPS-stimulated PMA-differetiated THP-1 cells, as evidenced by the decreased expression of iNOS, COX2, IL-1β, IL-6 and TNF-a, and the mechanism involves the inhibition of NF-r,B activation and the phosphorylation of the MAPK signal pathway.