method, including Raman and fluorescence, has attracted great attention in in vivo imaging due to their superior spatial resolution and sensitivity. [3] Especially, Raman imaging is a powerful vibrational optical spectroscopic technique and provides specific fingerprint information for a wide range of target molecules with ultranarrow spectral widths. These endowed Raman technology with advantage in imaging substances with overlapping fluorescence spectra and imaging in complex biological environments. Raman imaging is also highlighted with outstanding ability to tackle photobleaching and photodegradation, and thus suitable for long-term imaging. [2d,4] Raman imaging has shown great potential in diagnosis of cancers and visualization of various biological processes. To our knowledge, Raman probes for in vivo imaging are limited to surface enhanced Raman spectroscopy (SERS) probes (Au, Ag, and Cu nanoparticles), vibrational probes (alkyne, nitrile, and C-D) and single-walled carbon nanotube (SWNT) resonance Raman probes. [4a,5] Polymers, as materials with excellent biocompatibility, are expected to be a new generation of probes for in vivo Raman imaging. However, very few polymers have been reported to date as probes for high-sensitive in vivo Raman imaging, presumably because of the following reasons: i) the Raman signals of the developed polymers are intrinsically weak; and ii) the generated strong fluorescence background under excitation will interfere with the Raman signals. [6] To overcome these shortcomings, polymers were doped with other substances to increase the Raman signal intensity and reduce fluorescence. For example, polymers were coated on the surface of Au nanoparticles to enhance their Raman signals, based on the SERS effects. [6a] Other studies doped polymers with polydopamine to quench fluorescence and improve Raman signal intensity of polymers through an intermolecular energy transfer process. [6b] Nevertheless, the doping approach merely provided limited Raman signal enhancement for polymers, and these doped polymeric probes still failed to achieve high-resolution and sensitive in vivo imaging. Taken together, exploration of polymers as Raman imaging is a powerful tool for the diagnosis of cancers and visualization of various biological processes. Polymers possessing excellent biocompatibility are promising probes for Raman imaging. However, few polymers are reported to serve as Raman probes for in vivo imaging, mainly due to the intrinsic weak Raman signal intensity and fluorescence interference of these polymers. Herein, a poly(indacenodithiophene-benzothiadiazole) (IDT-BT) polymer is presented, which emits unprecedentedly strong Raman signals under the near-infrared wavelength (785 nm) excitation, thus functioning as a Raman probe for ultrasensitive in vivo Raman imaging. Further mechanistic studies unveil that the unique Raman feature of the IDT-BT polymer relies on molecularly regulating its absorbance edge adjacent to the desired excitation wavelength, thus avoiding fluorescence i...