Lithium ion dynamics in Li4+x Ti5O12 spinel are investigated from first principles calculations. The diffusion pathways are optimized and the energy barriers of lithium migration under four types of dilute defect extremes: Li4+δ Ti5O12, Li4−δ Ti5O12, Li7+δ Ti5O12 and Li7−δ Ti5O12 (δ ≪1) are calculated with the nudged elastic band method. Results show that lithium diffusion in the charged state (energy barriers are 1.0 and 0.7eV for interstitial Li and Li vacancy diffusion, respectively) is much slower than in the discharged state (energy barriers are 0.13 and 0.35eV for interstitial Li and Li vacancy diffusion, respectively). The diffusion coefficients are evaluated based on lattice gas model and hopping mechanism. The obtained results are compared with available experimental data within a two-phase co-existence framework.