It has long been appreciated that adequate nutrition is required for proper immune function and it is now recognized that dietary components contribute to modulation of immune cells, subsequently impacting the whole body's response during an immune challenge. Macrophage activation plays a critical role in the immune system and directs the brain-based response of the neuroimmune system, in particular that of social behavior. However, it is not well understood the role that diet, in the context of adequate nutrition, plays in macrophage activation, and thus, the social behavioral response of the neuroimmune system. Macrophage activation encompasses a wide range of phenotypes, from classical to alternative activation. Cytokines in the local microenvironment influence the activation state of macrophages. During activation of the neuroimmune system, antigen presenting cells, such as macrophages, produce cytokines that mediate communication of the peripheral immune status to the brain. This cytokine network establishes a bi-directional communication between the innate immune system and the central nervous system. Cytokine signaling in the brain leads to an organized change in behavior of the host, which represents an alteration in motivational priorities. This literature review focuses on information related to the ability of diet-related diseases, obesity and type 2 diabetes, to effect the activation of macrophages and the subsequent neuroimmune system response Chapters 2 through 5 establish that (1) leptin is key in behavioral recovery from hypoxia, which is up-regulated in obesity, and that the obesity-induced increase in systemic and adipose tissue macrophage IL-1 receptor antagonist (IL-1RA) hastens recovery from hypoxia. (2) Hyperglycemia associated with type 2 diabetes activates the p38 arm of the MAPK augmenting LPS-induced production of TNF-alpha from peritoneal macrophages. (3) Soluble fiber induces alternative activation of peritoneal macrophages, improving the behavioral response to infection in a manner dependent on IL-4. Taken together, these findings indicate that macrophages are influenced by diet resulting in an altered cytokine response, consequently modifying the social behavioral response to neuroimmune system activation. Importantly, these studies demonstrate that even within the context of adequate nutrition, diet influences the status of the immune system. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]