Curcuma comosa Roxb. is a medicinal plant that has traditionally been used in Thailand for treatment of inflammation in postpartum uterine bleeding. The purpose of this study was to evaluate its anti-inflammatory effects using peripheral blood mononuclear cells (PBMC) and human pro-monocytic cell line (U937). Pretreatment with hexane or ethanol extract or two diarylhepatanoids (5-hydroxy-7-(4-hydroxyphenyl)-1-phenyl-(1E)-1-heptene and 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene) of C. comosa significantly decreased the release of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta, from phorbol-12-myristate-13-acetate (PMA)-stimulated PBMC and U937 cells. In PMA-stimulated U937 cells, the two C. comosa diarylhepatanoids reduced the expression of TNF-alpha and suppressed expression of IkappaB kinase and activation of nuclear factor kappa B. These results indicated that C. comosa and its diarylheptanoids have anti-inflammatory properties which could be exploited for clinical use.