This paper presents the results of density functional theory calculations of the defect formation enthalpies of Frenkel and Schottky defects in rutile TiO2. The calculations are performed within the generalized gradient, supercell, and pseudopotential approximations and predict that Frenkel defects are more energetically favorable in TiO2 than Schottky defects. The calculations also indicate that both Frenkel and Schottky defects prefer to cluster together rather than spread out across the unit cell. Possible diffusion routes for interstitial Ti atoms are investigated and strong anisotropy in interstitial diffusion in TiO2 is supported by the results.