Microtubule and caveolin have common properties in intracellular trafficking and the regulation of cellular growth. Overexpression of caveolin in vascular smooth muscle cells increased the polymer form of microtubule without changing in the total amount of tubulin, and downregulation of caveolin decreased the polymer form of microtubule. Fractionation of cellular proteins followed by immunodetection as well as immunostaining of caveolin and microtubule revealed that caveolin and a portion of microtubule were co-localized in caveolar fractions. A caveolin scaffolding domain peptide, which mimics caveolin function, did not alter the polymerization of microtubule in vitro, but dramatically inhibited the depolymerization of microtubule induced by stathmin, a microtubule destabilizing protein, which was also found in caveolar fractions. Accordingly, it is most likely that caveolin increased the polymer form of microtubule through the inhibition of a microtubule destabilizer, stathmin, suggesting a novel role of caveolin in regulating cellular network and trafficking.