Background: Marantodes pumilum is traditionally used for dysentery, gonorrhea, and sickness in the bones. Previous studies revealed its antibacterial and xanthine oxidase inhibitory activities. Objective: To evaluate the inhibitory effects of three M. pumilum varieties on the secretion of lipopolysaccharide (LPS)- and monosodium urate crystal (MSU)-induced cytokines and plasma prostaglandin E2 (PGE2) in vitro. Materials and Methods: The leaves and roots of M. pumilum var. alata (MPA), M. pumilum var. pumila (MPP), and M. pumilum var. lanceolata (MPL) were successively extracted with dichloromethane (DCM), methanol, and water. Human peripheral blood mononuclear cells and ELISA technique were used for the cytokine assay, whereas human plasma and radioimmunoassay technique were used in the PGE2assay. Flavonoids content was determined using a reversed-phase high-performance liquid chromatography. Results: DCM extract of MPL roots showed the highest inhibition of LPS-stimulated cytokine secretion with IC50values of 29.87, 7.62, 5.84, 25.33, and 5.40 μ g/mL for interleukin (IL)-1α , IL-1β , IL-6, IL-8, and tumor necrosis factor (TNF)-α , respectively; while that of plasma PGE2 secretion was given by DCM extract of MPP roots (IC50 31.10 μ g/mL). Similarly, the DCM extract of MPL roots demonstrated the highest inhibition against MSU-stimulated IL-1α , IL-1β , IL-6, IL-8, TNF-α , and PGE2 secretion with IC50values of 11.2, 8.92, 12.29, 49.51, 9.60, and 31.58 μ g/mL, respectively. Apigenin in DCM extracts of MPL (0.051 mg/g) and MPP (0.064 mg/g) roots could be responsible for the strong inhibitory activity against IL-1β , IL-6, TNF-α , and PGE2. Conclusion: The results suggested that DCM extracts of MPL and MPP roots are potential anti-inflammatory agents by inhibiting the secretion of LPS- and MSU-stimulated pro-inflammatory cytokines and PGE2.