Human nutrient metabolism, developed millions of years ago, is anachronistic. Adaptive features that offered survival advantages are now great liabilities. The current dietary pattern, coupled with massively reduced physical activities, causes an epidemic of obesity and chronic metabolic diseases, such as type 2 diabetes mellitus. Chronic inflammation is a major contributing factor to the initiation and progression of most metabolic and cardiovascular diseases. Among all components of an innate immune system, due to their dual roles as phagocytic as well as antigen-presenting cells, macrophages play an important role in the regulation of inflammatory responses, affecting the body’s microenvironment and homeostasis. Earlier studies have established the beneficial, anti-inflammatory effects of whole body vibration (WBV) as a partial exercise mimetic, including reversing the effects of glucose intolerance and hepatic steatosis. Here for the first time, we describe potential mechanisms by which WBV may improve metabolic status and ameliorate the adverse consequences through macrophage polarization and altering the fecal microbiome.