In order to ensure pipeline commissioning safety and avoid security risks because of the direct contact between the air and oil, a progress of water isolation was necessary. And how to determine the amount of optimal isolation medium is becoming a new subject. The factors affecting the isolation medium quantity from the point of commissioning process was analyzed and a model to calculate the amount of isolation medium and the mixed oil quantity in a long slope pipeline was built while commissioning, based on existing empirical models, combined with field data. The relative error was in the acceptable range.