Monoamines have been known to mediate cellular immune responses such as hemocyte nodulation and phagocytosis in some insects. Eicosanoids also mediate the cellular immune reactions responsible for clearing bacterial infection from hemolymph circulation in various insects. In this study, we investigated a functional relationship of both mediators in expressing hemocyte nodulation and phagocytosis of fifth instar larvae of the beet armyworm, Spodoptera exigua. Addition of octopamine or serotonin along with bacteria enhanced hemocyte nodulation and phagocytosis of S. exigua larvae. Phentolamine (octopamine inhibitor) and ketanserin (serotonin inhibitor) suppressed hemocyte nodulation and phagocytosis of S. exigua in response to a bacterial challenge. Each inhibitory effect of both monoamine inhibitors was recovered by addition of either octopamine or serotonin, suggesting their independent signaling pathways. Both inhibitor effects were also recovered by addition of arachidonic acid (a precursor of eicosanoid biosynthesis). Furthermore, the stimulatory effects of monoamines on the cellular immune responses were prevented by addition of dexamethasone (a specific phospholipase A2). However, the inhibitory effect of dexamethasone was not recovered by excess amounts of monoamines. These results suggest that monoamines mediate hemocyte nodulation and phagocytosis through a downstream eicosanoid signal pathway in S. exigua.