Photoacoustic imaging is gaining great attention in the medical world due to its significant potential for clinical translation. Light excitation in the second near-infrared (NIR-II) window (1000-1350 nm) has resolution and penetration depth suitable for several clinical applications. However, the significant challenge exists for clinical translation because of the absence of notable intrinsic chromophores in this clinically significant optical range to generate diagnostic images. Methods: We present newly developed a biocompatible nickel dithiolene-based polymeric nanoparticle (NiPNP), which have a strong and sharp absorption peak at 1064 nm, as a photoacoustic contrast agent to boost specific absorbance in the NIR-II window for in vivo deep tissue imaging. Results: We confirm the enhanced PA signal by NiPNP's strong light absorption in the NIR-II window (287% higher than that of NIR-I) and deep tissue imaging capability (~5.1 cm) through in vitro experiment. We have successfully acquired diagnostic-quality in vivo photoacoustic images in deep tissue (~3.4 cm) of sentinel lymph nodes, gastrointestinal tracts, and bladders of live rats by using clinically viable imaging system. Conclusions: Our results prove that with strong absorption in the NIR-II window and with deeper imaging depth, the clinical translation of photoacoustic imaging with NiPNP is feasible for preclinical studies and thus would facilitate further clinical investigations.