The numerical simulation for the trans-scale fatigue failure process of TB5 titanium alloy plate specimens from the initial micro-defect to the macroscopic fatigue fracture is investigated. The fatigue damage degree can be represented by the restraining stresses. The micro/macro fatigue failure process can be described by the restraining stress zone crack model. Taking the micro/macro trans-scale strain energy density factor as a controlling parameter for the fatigue crack propagation, a micro/macro trans-scale numerical simulation approach for the fatigue process is developed. Adopting three scaling functions and the size of initial micro-defects at the fatigue source position, the influence of microscopic effects on the fatigue lives of specimens can be taken into account. The numerical simulation calculations are performed for the TB5 titanium alloy smooth plate specimens (stress concentration factor Kt=1) and the notched plate specimens (Kt=3). The results show that the calculated S-N curves can accurately fit the experimental S-N curves. With consideration of the microscopic effects, the scattered test data of fatigue lives of specimens can be re-produced by the proposed approach.