Abstract: For the long-time separate layer injection and production in Sazhong oilfield, the pore pressure distribution has varied greatly and abnormal high-pressure formations, normal pressure formations and un-derpressured formations coexist in the longitudinal profile of a single well. It has brought difficulty in main-taining the drilling construction safety, controlling drilling fluid and reservoir protection when drill infilling wells. In this paper, based on reservoir characteristics and development practice of this oilfield, the decompression laws of the different flooding pattern is found out and proper decom-pression program of the injec-tion wells, reasonable concentration of drilling fluid, right close time and the limited area are determined. Meanwhile, it has obtained the methods of pressure maintenance in high-permeability and low-pressure zone. Through controlling wellhead pressure of the injection wells, it can blow down the interlayer pressure difference, decrease the drilling fluid concentration and reduce the reservoir pollution. This research is important to the reservoir protection and improvement of the quality of drilling projects.