Cryptolepis sanguinoleta is a shrub used in West Africa for the treatment of fevers, and inflammatory conditions. In the present study the effect of the crude methanolic root extract of C. sanguinoleta on prostaglandin E2 (PGE2) release from LPS-stimulated human primary monocytes was investigated using an enzyme immunoassay. The effects of the extract on COX -2, I kappa Bα and p38 MAP Kinase proteins were also investigated. The extract (2.5-10µg/ml) produced a dose-dependent inhibition of LPS - induced PGE2 release in human primary monocytes. Western blot experiments showed that the extract inhibited LPS - induced COX -2 expression, as well as LPS - induced activation of p38 MAP kinase. However, the extract did not prevent LPS-induced I kappa Bα degradation in these cells. This study has therefore established in vitro potential anti - inflammatory properties of the root of C. sanguinoleta in LPS - stimulated human primary monocytes. It is suggested that the inhibition of LPS - induced PGE production in these cells by the root extract of C. sanguinoleta is mediated through inhibition of COX -2 protein. We further postulate that the observed effects may be dependent on the inhibition of p38 MAP kinase activation.