We previously reported that oridonin, a major component isolated from the plant Rabdosia rubescens HEMSL, induced apoptosis in human melanoma A375-S2 and cervical cancer HeLa cells. In the present study, oridonin was first evaluated for its effect on phagocytosis of apoptotic cells by macrophages. Preincubation of human histocytic lymphoma U937 cell-derived macrophages with 2.7mM oridonin significantly augmented phagocytosis of UV-irradiated (2.4 J/cm2, 4 min) U937 cells undergoing apoptosis in a dose-and time-dependent manner. However, less effect on synthetic fluoresbrite microspheres indicated that enhancement of apoptotic U937 cell uptake by oridonin was a selective effect. The oridonin-augmented phagocytosis was attenuated by anti-human TNFa and IL-1b antisera, suggesting that TNFa and IL-1b participate in the phagocytosis by oridonin-treated U937 cell-derived macrophages. In addition, the similar effect of phagocytosis was observed in oridonin-treated human monocyte-derived macrophages at 4 d maturation. Taken together, oridonin facilitates the phagocytic activity against apoptotic cells through TNFa and IL-1b release, which may be contribute to its antitumor activities.