Abstract: The differential pressure method for leak detection is a kind of pressure variation leak detection techniques based on high precision differential pressure sensors. Leak detection of spacecraft propulsion systems can eliminate the use of accumulate chamber, if differential pressure method for leak detection is used. This paper develops a new differential pressure method for leak detection with an asymmetrical reference, estimates the sensitivity of this method on the condition of leak detection of spacecraft propulsion systems, and carries out experiments with this method under pressures 2 MPa and 20 MPa. The results indicate that the new method can meet the requirement for the total leakage rate of the spacecraft propulsion system.