Recently, several multidisciplinary projects have begun to model and simulate human physiological systems. However, the simulators for these models are often limited in terms of simulation type and lack of parallel computing support. In this paper we describe insilicoSim, an extendable simulation engine for performing parallel large scale biophysical simulations. We present three key components of the simulator for improving extensibility and performance. First, we demonstrate how a standardized plugin interface allows for easy extension of the simulator to new types of input, output and simulation methods. We detail a technique for improving simulation performance by simplifying and compiling simulation related mathematical expressions into an internal byte code representation for fast evaluation. Finally, we describe the simulation object manager which allows for shared object access between simulation interfaces while transparently performing parallel synchronization. We demonstrate the effectiveness of these methods by simulating several models on both serial and parallel computing platforms.