based on molecular structure design to prepare amphoteric polymer fluid loss additive PADMS with properties of high temperature resistance and salt tolerance, AM, AMPS, DMDAAC and NVP were chosen as reactive monomers for quaternary copolymerization. The feasibility of molecular structure design of PADMS was proved by FITR and its adsorption capacity on clay particles was superior to sulfonated phenolic resin of SMP-II and SMP-III. After adding 2.0% PADMS, the apparent viscosity and plastic viscosity of the freshwater mud increased from 10.5 mPa·s to 35.0 mPa·s and from 5.0 mPa·s to 28.0 mPa·s, respectively, API filter loss decreased from 28.0 mL to 6.0 mL. The apparent viscosity and plastic viscosity is 17.5 mPa·s and 15.0 mPa·s, respectively, after aged for 16 h at the temperature of 200℃, and API filter loss decreased from 48.6 mL to 15.6mL. After adding 2.0% PADMS, the apparent viscosity and plastic viscosity of the compounded brine mud increased from 3.0 mPa·s to 19.5 mPa·s and from 1.5 mPa·s to 15.0 mPa·s, respectively. The viscosity of the compounded brine mud also increased with the increas of PADMS content after aged for 16 h at the temperature of 200℃. After adding 2.0% PADMS, API filter loss of pre and post aging decreased respectively from 88.0 mL to 8.2 mL and from 168.0 mL to 54.6 mL. HTHP filter loss decreased from severe loss to 86.4 mL.