Contrast agents are attracting a great deal of attention in photoacoustic imaging. Here we introduce an exogenous contrast agent that provides high photoacoustic signal amplitude at the near-infrared wavelength. Our agents consist of Indocyanine green (ICG) and phospholipid–polyethylene glycol (PL–PEG), entitled ICG–PL–PEG nanoparticles. These nanoparticles have overcome numerous limitations of ICG, such as poor aqueous stability, concentration-dependent aggregation and lack of target specificity. ICG–PL–PEG nanoparticles are biocompatible and relatively nontoxic. All the components of ICG–PL–PEG nanoparticles have been approved for human use. Upon pulsed laser irradiation, the nanoparticles are more efficient in producing photoacoustic waves than ICG alone. The results showed that ICG–PL–PEG nanoparticles act as good contrast agents for photoacoustic imaging. These unique ICG–PL–PEG nanoparticles have great potential in clinical applications.