The objectives of this study were to investigate the effects of chlorophyll-related compounds (CRCs) and chlorophyll (Chl) a + b on inflammation in human aortic endothelial cells. Adhesion molecule expression and interleukin (IL)- 8, nuclear factor (NF)-${kappa}B$ p65 protein, and NF-${kappa}B$ and activator protein (AP)-1 DNA binding were assessed. The effects of CRCs on inflammatory signaling pathways of signal transducers and activators of transcription 3 (STAT3) and mothers against decapentaplegic homolog 4, respectively induced by IL-6 and transforming growth factor (TGF)-${eta}$, in human aortic smooth muscle cells cultured in vitro were also investigated. HAECs were pretreated with 10 ${mu}M$ of CRCs, Chl a + b, and aspirin (Asp) for 18 h followed by tumor necrosis factor (TNF)-${alpha}$ (2 ng/mL) for 6 h, and U937 cell adhesion was determined. TNF-${alpha}$-induced monocyte-endothelial cell adhesion was significantly inhibited by CRCs. Moreover, CRCs and Chl a + b significantly attenuated vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and IL-8 expressions. Treatments also significantly decreased in NF-${kappa}B$ expression, DNA binding, and AP-1 DNA binding by CRCs and Asp. Thus, CRCs exert anti-inflammatory effects through modulation of NF-${kappa}B$ and AP-1 signaling. Ten micromoles of CRCs and Asp upregulated the expression of mothers against decapentaplegic homolog 4 (Drosophila) (SMAD4) in the ${eta}$ receptor signaling pathway, and SMAD3/4 transcription activity was also increased. Ten micromoles of CRCs were able to potently inhibit STAT3-binding activity by repressing IL-6-induced STAT3 expression. Our results provide a potential mechanism that explains the anti-inflammatory activities of these CRCs.