Evidence exists that interleukin (IL)-1β is involved in pancreatic β-cell damage, whereas TNF-α appears to be a key molecule in peripheral insulin resistance. Although increased plasma levels of IL-6 are seen in individuals with type 2 diabetes, mechanistic studies suggest that moderate acute elevations in IL-6, as provoked by exercise, exert anti-inflammatory effects by an inhibition of TNF-α and by stimulating IL-1 receptor antagonist (ra), thereby limiting IL-1β signaling. A number of medical treatments have anti-inflammatory effects. IL-1 antagonists have been tested in clinical studies and appear very promising. Also, there is a potential for anti-TNF-α strategies and salsalate has been shown to improve insulin sensitivity in clinical trials. Furthermore, the anti-inflammatory potential of statins, antagonists of the renin-angiotensin system, and glucose-lowering agents are discussed. While waiting for the outcome of long-term clinical pharmacological trials, it should be emphasized that physical activity represents a natural strong anti-inflammatory intervention with little or no side effects.