Motivated by the unusual behavior of TiO2 films seen in electrical stress and defect annealing experiments, we studied the energy profile for forming a Frenkel defect in rutile TiO2, using first-principles calculations with a nudged-elastic-band method. We found strongly asymmetric diffusion barriers. The Frenkel pairs with small separation are exceedingly short-lived: the Ti interstitial position nearest to the the Ti vacancy is separated by only a 0.15eV barrier, and the next-nearest interstitial position is dynamically unstable. The formation enthalpies of Frenkel pairs with larger separation gradually vary between 4.2 and 5.0 eV, separated by 0.3-0.4eV barriers along the (001) direction. Contrary to some previous studies, we do not find Frenkel configurations with tetrahedrally bonded Ti interstitials. The very low barriers for Frenkel defect evolution are consistent with the observations from the electrical stress damage annealing experiments.