In this paper, a novel approach to constructing flexible Lyapunov inequalities is developed for establishing Input-to-State Stability (ISS) of interconnection of nonlinear time-varying systems. it aims at a useful tool for using nonlinear small-gain conditions by allowing some flexibility in Lyapunov inequalities each subsystem is to satisfy. In the application of the ISS small-gain "theorem", achieving a Lyapunov inequality conforming to a nonlinear small-gain "condition" is not a straightforward task. The proposed technique Provides us with many Lyapunov inequalities with which a single trade-off condition between subsystems gains can establish the ISS property of the interconnected system. Proofs are based on explicit construction of Lyapunov functions. (c) 2008 Elsevier Ltd. All rights reserved.