In fracture treatment with external fixators, the inter-fragmentary movements at the fracture site affect the fracture healing process, and these movements are highly related to the stiffness of external fixation systems. Therefore, in order to provide the optimal fracture healing at the fracture site, it is essential to understand the relationship between the stiffness and the system configurations in external fixation system. In this study we investigated the influences of system configuration parameters on the stiffness in the finite element analysis of an external fixation system of a long bone. The system alignment, the geometric and the material non-linearity of the pin, the joint stiffness and the callus formation were considered in the finite element model. In the first, the system stiffness of the developed finite element model was compared with the experiment data for model validation. The consideration of the joint stiffness and nonlinearity of the model improved the system stiffness results. The joint stiffness, the non-alignment of the system decreased the system stiffness while the callus formation increased the system stiffness. The present results provided the biomechanical basis of rational guidelines for design improvements of external fixators and pre-op. planning to maximize the system stiffness in fracture surgery.