A new molecular thermodynamic model for describing the swelling behavior of thermo-sensitive hydrogels was developed. The model consists of two terms. One is the contribution of the mixing of hydrogel network and water, which is dependent on the local polymer concentration and the interaction between polymer segment and solvent. A closed packed lattice model for polymer solution developed by Yang et al. was adopted for this term. The other is the elastic contribution derived from the network elasticity, which is dependent on the cross-linking degree of gel network. The elastic Gibbs energy model based on the Gaussian chain model developed by Flory was adopted. The model equation has two parameters. One is an energy parameter F reflecting the interaction between water and gel network, the other is a size parameter V* that represents the cross-linking degree of the hydrogel. When the energy parameter F is expressed as a quadratic of inverse temperature, this model can describe the swelling equilibrium behavior of neutral thermo-sensitive hydrogels quite well. The influences of model parameters were discussed in details. The experimental swelling curves of two kinds of polyacrylamide-based gels were correlated and good agreement was obtained. (c) 2007 Elsevier B.V. All rights reserved.