The present work is an attempt to explore immunomodulatory activity of some natural products taking into account the major cellular immune reaction, nodulation, in the short horned grasshopper Poekilocerus pictus. It has been shown that two different groups of natural products i.e. quinones, juglone and plumbagin and azadirachtins, neemazal and TN MP-100 inhibit the nodulation reaction against four different species of bacteria, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and bacteria isolated from the gut of P. pictus itself (‘self bacteria’),used to artificially infect the grasshopper. Role of eicosanoid in mediation of nodule formation has been shown by studying the effects of eicosanoid inhibitor dexamethasone and rescue experiments using the precursor, arachidonic acid. Significant reduction in the number of nodules by dexamethasone and their restoration by arachidonic acid has shown that eicosanoids function for nodulation in P. pictus. Most interesting result of the present work has been revealed by the fact that all the four natural products inhibit nodule formation in P. pictus, which would lead to impaired immunity in the insect. These results can be exploited in insect pest management by inducing immunodeficiency.