In this paper, we consider the existence conditions of periodic oscillations in large-scale cyclic gene regulatory networks. Using the Poincare-Bendixson theorem for cyclic systems, we first show that the local instability of an equilibrium point implies the existence of periodic oscillations. We then derive the graphical and its equivalent analytic criteria for the existence of periodic oscillations based on local instability analysis. These criteria have a remarkable feature that they can be applied systematically to a large-scale cyclic gene regulatory network consisting of any number of genes. The latter part of this paper is devoted to analyze the relation between an equilibrium point and the biochemical parameters. This leads to an analytic existence criterion that explicitly takes the dependence of the equilibrium state on biochemical parameters into account, which is often overlooked in nonlinear system analyses. In particular, the novel physical quantities that are essential for determining the existence of periodic oscillations are obtained based on the rigorous analytic criterion. (C) 2011 Elsevier Ltd. All rights reserved.