Background: Recently, the biceps was rerouted into a newly fabricated bicipital groove for in situ superior capsular reconstruction (SCR), resulting in promising time-zero cadaveric and clinical outcomes. However, no studies have determined the in vivo biomechanical and histological processes after the biceps is transposed to a nonanatomic position. Purpose: To explore the in vivo biomechanical and histological processes of the rerouting biceps tendon to treat chronic irreparable rotator cuff tears (IRCTs) in a rabbit model. Study Design: Controlled laboratory study. Methods: A total of 94 skeletally mature male rabbits were used to create a chronic IRCT model in the supraspinatus tendon. Then, the biceps rerouting procedures were performed in rabbits with chronic IRCT. Eighteen rabbits were sacrificed at 1, 3, 6, 9, and 12 weeks postoperatively for biomechanical testing, micro—computed tomography scanning, and histological analysis. The biomechanical and histological changes of intra- and extra-articular portions of the rerouting biceps were evaluated at each time point, with the contralateral native superior capsule (NSC) and the native biceps (NB) as controls, respectively. The morphology and bone formation of the fabricated bicipital grooves were evaluated, with native grooves as controls. Results: The intra-articular rerouting biceps tendon was progressively remodeled over time, displaying denser fibers and more mature collagen than those of the NSC, with gradual improvements in the tendon-to-bone healing interface from 6 to 12 weeks. Consequently, the failure load and stiffness of the intra-articular rerouting biceps portion increased with time and were significantly higher than those of the NSC from 9 weeks. Similarly, the extra-articular portion of the rerouting biceps progressively healed into a new bicipital groove, as demonstrated by a smaller tendon-to-bone interface from 6 to 12 weeks, resulting in greater failure load and stiffness at 9 and 12 weeks than those of the NB attachment. The newly fabricated bicipital groove showed similar morphology to that of the native groove with sufficient trabecular bone formed underneath. Conclusion: The rerouting biceps could progressively remodel and heal into the newly fabricated bicipital groove over time, resulting in greater biomechanical performances in intra- and extra-articular portions than the NSC and the NB attachment. Clinical Relevance: The biceps rerouting technique may be a feasible procedure to perform in situ SCR to treat IRCT in the future clinical practice; however, more clinical evidence is required.