Cryptolepis sanguinolenta (Lindl.) Schltr. is a shrub used in West Africa for the treatment of fevers and inflammatory conditions. In the present study the effect of the root extract of C. sanguinolenta on prostaglandin E2 (PGE2) release from IL-1β-stimulated SK-N-SH neurons was investigated. The effects of the extract on COX-2 and p38 MAP Kinase proteins were also investigated. C. sanguinolenta (2.5-10µg/ml) produced a dose-dependent inhibition of IL-1β-induced PGE2 release from SK-N-SH cells. Western blot experiments revealed that the extract (5-20µg/ml) inhibited IL-1β-induced COX -2 and p38 expressions in these cells. The present work provides evidence that C. sanguinolenta root extract inhibits the production of PGE2 in IL-1β-stimulated neuroblastoma cells through inhibition of COX-2 protein. It is suggested that the observed effects may be dependent on the inhibition of p38 MAP Kinase activation.