Any disruption of the lymphatic system due to trauma or injury can lead to edema. There is no effective cure for lymphedema, partly because predictive knowledge of lymphatic system reactions to interventions is lacking. A well-developed model of the system could greatly improve our understanding of its function. Lymphangions, defined as the vessel segment between two valves, are the individual pumping units. Based on our previous lumped-parameter model of a chain of lymphangions, this study aimed to identify the parameters that affect the system output the most using a sensitivity analysis. The system was highly sensitive to minimum valve resistance, such that variations in this parameter caused an order-of-magnitude change in time-average flow rate for certain values of imposed pressure difference. Average flow rate doubled when contraction frequency was increased within its physiological range. Optimum lymphangion length was found to be some 13–14.5 diameters. A peak of time-average flow rate occurred when transmural pressure was such that the pressure-diameter loop for active contractions was centered near maximum passive vessel compliance. Increasing the number of lymphangions in the chain improved the pumping in the presence of larger adverse pressure differences. For a given pressure difference, the optimal number of lymphangions increased with the total vessel length. These results indicate that further experiments to estimate valve resistance more accurately are necessary. The existence of an optimal value of transmural pressure may provide additional guidelines for increasing pumping in areas affected by edema.