An improved Intelligent Single Particle Optimizer (ISPO) algorithm is proposed for 3D route planning of Unmanned Aerial Vehicles (UAVs). The ISPO algorithm is applied to the route planning, and the attracting effect between sub-vectors is introduced to the improved algorithm, which effectively overcomes the shortcoming that the algorithm is easy to fall into the locally optimal solution.Simulation experiments are carried out, in which the improved ISPO algorithm, the Particle Swarm Optimizer (PSO) algorithm with dynamic inertia coefficient and the PSO with reverse-learning and local-learning capabilities (RLPSO) are applied to the route planning. The simulation results show that the improved ISPO algorithm has the best searching precision and ability in the route planning, and its efficiency is higher than that of the other two algorithms.