Nitric oxide (NO) is one of the most important components of blood vessels’ health. NO is a gas compound with different physiological and biochemical effects on the body. It is a free radical, which plays as an endogenous and endothelium relaxing factor. NO has a protective role in digestive system which also plays different roles in the immune system as a mediator of immunity; e.g. regulating immune response, and stimulation and suppression of the immune system. NO has three isoforms each of which is expressed by a special gene. These isoforms include neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) which both are depending on calcium and calmodulin. The third isoform, independent on calcium and calmodulin, is inducible nitric oxide synthase (iNOS). Even in special conditions such as renal ischemia-reperfusion, it has been shown that high iNOS and low eNOS levels are involved in increased inflammation and connective tissue damage.

Metformin is one of the oldest and commonly used blood sugar lowering drugs, having limited side effects and used as the first line treatment in patients suffering from diabetes mellitus. Moreover, various studies have emphasized on the anti-inflammatory and antioxidant role of metformin, with multiple mechanisms, which activation of AMPK by metformin has had a key role in many of them. During the searches on the internet websites of PubMed, Elsevier, Google Scholar, and Science Direct, 76 papers related to the anti-inflammatory and antioxidant role of metformin were selected and reviewed since 2003 to 2017. At the cellular level, metformin suppresses the inflammation in many cases and reduces or eliminates inflammatory factors mainly through dependent mechanisms and sometimes independent of AMPK at the cellular level and through other ways at the systematic levels. It is also effective in reducing the level of oxidative stress factors by regulating the antioxidant system of the cell. All evidence suggests the antioxidant and anti-inflammatory role of metformin in various conditions. Metformin can be an appropriate treatment option for many diseases, which inflammatory processes and oxidative stress play a role in their pathogenesis.