Animal models of traumatic brain injury (TBI) have shown that impaired motor and cognitive function can be improved by physical exercise. However, not each animal with TBI can be well rehabilitated at the same training intensity due to a high inter-subject variability. Hence, this paper presents a two-stage wheel-based mixed-mode rehabilitation mechanism by which the effect of stress on the rehabilitation performance was investigated. The mixed-mode rehabilitation mechanism consists of a two-week adaptive and a one-week voluntary rehabilitation program as Stages 1 and 2, respectively. In Stage 1, the common over and undertraining problem were completely resolved due to the adaptive design, and rats ran voluntarily over a 30-min duration in Stage 2. The training intensity adapted to the physical condition of all the TBI rats at all times in Stage 1, and then the self-motivated running rats were further rehabilitated under the lowest level of stress in Stage 2. For comparison purposes, another group of rats took a 3-week adaptive rehabilitation program. During the 3-week program, the rehabilitation performance of the rats were assessed using modified neurologic severity score (mNSS) and an 8-arm radial maze. Surprisingly, the group taking the mixed mode program turned out to outperform its counterpart in terms of mNSS. The mixed-mode rehabilitation mechanism was validated as an effective and efficient way to help rats restore motor, neurological and cognitive function after TBI. It was validated that the rehabilitation performance can be optimized under the lowest level of stress.