Some inhibitors of tyrosine kinase, as imatinib, erlotinib and sunitinib have antihyperglycemic effects but the mechanisms are not totally clear. It is well established that insulin resistance and beta-cell failure are hallmarks of type 2 diabetes mellitus (DM2). The present review will discuss the molecular mechanisms that account for insulin resistance and beta-cell failure in DM2, and also the effect of tyrosine kinase inhibitors in these processes. A better understanding of how these drugs improve the two most important mechanisms of DM2 associated with suggestions of clinical studies will lead to improve the treatment of this disease.22751-63