The objective of this study is to develop a mathematical model for simulating the thermal physiological responses of clothed infants. By modifying and integrating Gagge's two-node model and Stolwijk's multi-node model, and coupled with the model of dynamic couple heat and moisture transfer in functional clothing, a new seven-node thermoregulation model for closed infants was developed. A series of preliminary numerical test were carried out for naked and clothed infant. The prediction of the new model was compared with the published data, the comparison results demonstrate that the model has good potential predictability.