Abstract: The running characteristic of oil pipelines injected with depressant (PPD-ed) and pump operating characteristic are analyzed and an operation optimization model for oil pipelines is established. On the basis of combining genetic algorithm and simulated annealing algorithm, hybrid genetic algorithm is created, which is adopted to solve the optimization model of oil pipeline operation. The result shows that the optimal operation cost of oil pipeline after depressant injection is reduced by 8.17% compared to that without depressant. It is considered that the optimal operation scheme is helpful for instructing the real productive operation of oil pipelines.