The aim of this study was to evaluate the effect of salidroside on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production in RAW 264.7 macrophages and related anti-inflammatory mechanism. $PGE_2$ production was measured by enzyme-linked immunosorbent assay (ELISA); NO production was tested by Griess reagent. Inducible nitric oxidesynthase (iNOS) and COX-2 were determined by RT-PCR and Western blot analysis; $I{kappa}B$ and P-$I{kappa}B$ protein express were detected by Western blot analysis; cytosolic free $Ca^{2+}$([$Ca^{2+}$]i)was measured by a fluorescent microscope. The data showed salidroside inhibited LPS-induced NO and $PGE^2$ production and reduced iNOS and COX-2 protein expression in RAW 264.7 macrophages. Consistent with these observations, salidroside inhibited LPS-induced cytosolic free $Ca^{2+}$ concentration ([$Ca^{2+}$]i) elevation. In addition, we further investigated signal transduction mechanisms and found that the activation of NF-${kappa}B$ was suppressed by salidroside in a dose-dependent manner. These results suggest that salidroside suppresses NO and $PGE_2$ production by inhibiting iNOS and COX-2 protein expression, level of [$Ca^{2+}$]i, and activation of NF-${kappa}B$ signal transduction pathway.