Rhubarb is the well-known and frequently used herbal medicine for the treatment of constipation, inflammation, and cancer. As described in the Korea and Chinese Pharmacopoeia, rhubarb consists of the roots and rhizomes of Rheum palmatum, R. officinale, and R. tanguticum. However, the pharmacological differences among rhubarb have not been scientifically established. In the present study, we investigated and compared the inhibitory effects of 70% ethanolic extracts from R. palmatum (RPE), R. officinale (ROE), R. nobile (RNE), and R. franzenbachii (RFE) on the production of inflammatory mediators, nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), interlukin-1beta ($IL-1{eta}$), and tumor necrosis factor-alpha ($TNF-{alpha}$) in RAW 264.7 macrophage cells. ROE, RNE, and RFE significantly inhibited the release of NO, $PGE_2$, $IL-1{eta}$, and $TNF-{alpha}$. RPE significantly reduced the release of $IL-1{eta}$, but not NO, $PGE_2$, and $TNF-{alpha}$. Overall, RFE was found to inhibit the release of $PGE_2$ and $IL-1{eta}$, to a far greater degree than RPE, ROE, and RNE. Our results indicate that RFE possess the strongest anti-inflammatory activity among 4 tested rhubarb.