In daily medical operation, penetration of syringe needles into the rubber plug, usually produces micro particles due to plug failure, which has been attracted increasing attentions for patient’s health. In this work, the needle penetration is investigated experimentally and numerically, by focusing on penetration process. Firstly, mechanical behaviors of butyl rubber material are obtained experimentally, by performing various strain rate experiments based on Instron 5848 machine and Hopkinson tension bar technique. The distinct strain rate-dependence is found of rubber mechanic behaviors. Its constitutive relation and parameters are then determined, and used for numerical simulation work. Penetrations of traditional syringe needle are designed and experimented through butyl rubber plugs of vials. As a result, plug mass loss is obtained to investigate the micro particles’ generation. Finally, the finite element model is built based on Abaqus code, of which the smoothed particle hydrodynamics method is introduced for plug fracture behavior. Numerical simulations are performed for penetration process, and the results is basically consistent with the experiment. More accurate simulation work will be performed for detailed penetration responses, and even fracture dependence on needle configuration and so on.