Based on the literature review and experimental experience (Scheme 1), we found that the replacement of the triphenylamine (TPA) group with the tetraphenylethlene (TPE) group in D-A-D dyes can largely improve the QYs. Until now, few studies have systematically explained this intriguing phenomenon, while we rationally conjecture that this strategy can boost the QYs for NIR-II AIEgens for the following reasons. (1) The TPE group can weaken the D-A interaction to alleviate the TICT effect in the polar environment. (2) TPE has less trend of molecular motion in the aggregate state because the bulkier structure of TPE can bring more intermolecular interactions. (3) There are more covalent bonds attached to the C atom in TPE than the N atom in TPA, also resulting in a stronger RIM effect. The three factors may generate more stabilized excitons when using TPE as the donor group. Here, we designed and synthesized two NIR-II emissive AIEgens called TPE-BBT and TPEO-BBT by replacing the TPA group in TPA-BBT with the TPE group (Figure ). As expected, the photoluminescent nanoparticles (PLNPs) of TPE-BBT and TPEO-BBT showed much enhanced QYs, which were measured to be 31.5% and 23.9% vs. IR26 (QY = 0.5%), respectively. More importantly, the crystals of TPE-BBT demonstrated an absolute QY of 10.4%, which is the highest absolute QY reported so far. Single-crystal analysis and theoretical calculations revealed that the optimized D-A interaction and the higher rigidity of TPE-BBT in the aggregate state are the two key factors for its ultrahigh QY. This ultrahigh QY rendered TPE-BBT ideal material for NIR-II photoluminescence (PL) bioimaging. Moreover, TPE-BBT realized NIR-II chemiluminescence (CL) bioimaging, which can avoid the limitation of excitation light sources through successive CL resonance energy transfer (CRET) and Förster resonance energy transfer (FRET) processes. The ultrahigh QY of TPE-BBT ensured a high energy transfer efficiency and excellent continuous imaging for the local arthrosis inflammation detection in mice. Thus, this work revealed a promising strategy to design NIR-II dyes with high QYs and provided insights into the underlying mechanism.