* Equal contributors. Received March 9, 2014; Accepted April 10, 2014; Epub April 15, 2014; Published April 30, 2014 Abstract: In this study, 20 new derivatives of caffeic acid esters were synthesized and their inhibitory activities against the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages were deter- mined. Compounds 3l, 3r, 3s and 3t were found to decrease nitrite levels in a dose-dependent manner in LPS- induced cells and showed potent inhibitory activities against the NO production in RAW264.7 macrophages with IC 50 values of 7.4, 5.9, 3.3 and 2.2 μM, respectively. They could be selected as compromising compounds for the later pharmacological study.