AIM Oridonin, a bioactive diterpenoid isolated from Rabdosia rubescens, stimulated human U937 macrophage-like cells to engulf apoptotic cells by autophagy (efferocytosis) and inflammatory pathways.We tried to show the role of nitric oxide (NO) in this process.METHODS Antophagy was observed by MDC staining.Flow cytometric analysis was carried out to measure autophagy and NO production.Apoptosis of U937 cells was induced by UV irradiation and the efferocytesis was analysed by fluorescent microscopy.RESULTS Exposure of U937 cells to 2.5 μmol· L-1 oridonin up-regulated inducible nitric oxidesynthase (iNOS) expression and continuous endogenous generation of NO, which was reversed by pre-treatment with the inhibitors of nitric oxide synthase 1400W or L-NAME.NO donor sodium nitroprusside (SNP) and efferocytosis irritant lipopolysaccharide (LPS) could also exert NO generation and iNOS expression.Moreover, oridonin-induced stimulation of efferocytosis was significantly suppressed by 1400W or L-NAME.In addition, 1400W or L-NAME impaired oridonin-induced autophagy.Interleukin-1 β (IL-1β) was involved in oridonin-induced efferocytosis in U937 cells and interacted with NO to contribute to inflammatory responses.1400W or L-NAME blocked the secretion of IL-1β and the activation of NF-κB and COX-2.Provision of SNP or LPS in place of oridonin resulted in similar enhancement of efferocytosis, autophagy, the release of IL-1 β and the expresstion of signal protein.CONCLUSION NO augmented the oridonin-induced efferocytosis of apoptotic cells by mediating autophagy and activating the NF-κB-COX-2-IL-1β pathway.