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Elevated atmospheric CO2 (eCO(2)) and increased nitrogen (N) fertilization significantly change the nutritional quality of plants and influence the growth and development of insects. However, little is known about plant metabolism and plant-insect interactions under eCO(2) and increased N fertilization, especially C-4 plants. Thus, the combined effects of eCO(2) and increased N fertilization on maize-Ostrinia furnacalis interactions were tested in this study. Our data demonstrated that both eCO(2) and increased N fertilization increased starch content, while increased N fertilization promoted the N content in maize. The combined effects of eCO(2) and increased N fertilization did not influence the total non-structural carbohydrates (TNC):N ratio in maize. The jasmonic acid level of maize was enhanced by increased N fertilization and O. fumacalis infestation. The total phenolics content and defensive enzyme activities of maize increased under eCO(2), increased N fertilization and O. fumacalis infestation. Protective enzyme activities were enhanced, while digestive enzyme activities, mean relative growth rate, body mass and efficiency of conversion of ingested food decreased for O. furnacalis feeding on maize grown under eCO(2) and increased N fertilization. Therefore, eCO(2) and increased N fertilization increased starch and N accumulation, and did not influence the TNC:N ratio, however, eCO(2) and N promoted the resistance-related secondary metabolites (with or without O. fumacalis induced) of maize, which ultimately decreased the fitness of O. fumacalis to the host. These results will help to better understand the metabolic mechanisms of plants and the plant-insect interaction under eCO(2) and increased N fertilization in the context of future climate change scenarios.