Globalization of occidental way of life is leading to increasing prevalence of obesity and type 2 diabetes, the greatest pandemy of the XXI century. Type 2 diabetes is the result of peripheral insulin resistance and concomitant decreased β cell insulin secretion. Insulin resistance and cardiovascular disease share common pathophysiological mechanisms, as the chronic activation of the innate immune system. This system constitutes the first line of bodys defense and it is constituted by different barriers (epithelia, adipose tissue), and different blood and tissue components as macrophages, and neutrophils. Once activated, the innate immune system generates the acute phase response in which different acute phase proteins and cytokines are produced to fight against different aggressions as infections and traumatisms. The aim of this response is to eradicate these agents, to repair the harmed tissues, and, through increased insulin resistance, to optimize the energetic substrates, which will be drained to vital tissues and organs (i.e. brain and the immune system). Evolution pressures have led to survival of the fittest individuals, those with genetics that allows the best defense against infection and periods of famine. The initial evolutive advantages of increased inflammatory responses, hypersecretion of proinflammatory cytokines (TNF-α, interleukin (IL)-1 β, IL-6, IL-18, ....), and antiinflammatory molecules (adiponectin, sCD14), turn into chronic inflammation conditions, such as obesity and type 2 diabetes. Increasing evidence is reported according to which chronic inflammation precedes these conditions. The knowledge of how these metabolic pathways interact with the inflammatory cascade will facilitate new therapeutic approaches.