The diffusion equation in multiple-scattering media with photon density wave is a hotspot in the field of biomedical photonics. Considered the cubic boundary conditions,a second-order analytical solution of diffusion equation of photon density wave is presented. The relationship between the absorption coefficient and the flux is derived,for the flux can be easily obtained in practical experiments. Using this relationship and the optical properties of typical forearm tissue,the second-order simulation results are given. Compared with the results of first-order solution,second-order one is more accurate and the precision is greatly improved. This method proposed is applicable in the biomedical imaging of multiple-scattering media,and has many advantages in the imaging quality and spatial resolution.