We show that large-scale atmospheric inhomogeneities observed experimentally can significantly affect optical radiation propagation along long paths, and it is impossible to take into account this effect within the classical turbulence model. We suggest a new algorithm for numerical simulation of laser beam propagation along long low-inclined atmospheric paths with large-scale atmospheric inhomogeneities, which allows one to consider beam refraction and focusing at large-scale inhomogeneities along with beam distortions due to small-scale inhomogeneities and regular refraction in a vertical plane.