Abstract The powdered injection system (PowderJect) is a novel needle-free device for the delivery of micron DNA vaccines. The underlying principle is to harness energy from compressed Helium gas to accelerate a pre-measured dose of DNA vaccine coated in micro-gold particles to an appropriate momentum in order to penetrate the outer layer of the skin or mucosal tissue to achieve a biological effect. One of the latest PowderJect developments is the Venturi system, using the venturi effect to entrain micron-sized vaccines into an established quasi-steady supersonic jet flow and accelerate them towards the target. In this paper, we developed a physical–mathematical model to simulate fluid and particle transportation of a prototype Venturi device. The key features of the gas dynamics and gas–particle interaction are presented. The overall capability of the Venturi system for particle delivery is discussed.