Muscle contractions and insulin stimulate glucose transport into muscle by separate pathways. The contraction mediated increase in glucose transport is mediated by two mechanisms, one involves the activation of 5' AMP activated protein kinase (AMPK) the other involves the activation of calcium/calmodulin dependent protein kinase II (CAMKII). The steps leading from the activation of AMPK and CAMKII to the translocation of GLUT 4 to the cell surface have not been identified. Studies, using the tyrosine kinase inhibitor genistein, suggest that one or more tyrosine kinases could be involved in contraction-stimulated glucose transport. The purpose of the present study was to determine the involvement of tyrosine kinases in contraction-stimulated glucose transport in rat soleus and epitrochlearis muscles. Contraction-stimulated glucose transport was completely prevented by pretreatment with genistein (100 µM) and the related compound butein (100 µM). However the structurally distinct tyrosine kinase inhibitors PP2 and herbimycin did not reduce contraction stimulated glucose transport. Furthermore genistein and butein inhibited glucose transport even when muscles were exposed to these compounds after being stimulated to contract. Muscle contractions did not result in increases in tyrosine phosphorylation of proteins such as PYK2 and SRC. These results provide evidence that tyrosine kinases do not mediate contraction stimulated glucose transport and that the inhibitory effects of genistein on glucose transport result from direct inhibition of the glucose transporters at the cell surface.