This paper addresses the multi-scale modeling of human thermal regulation and the evaluation of human thermal comfort when the human body is dressed. A multi-scale model incorporating models of three-dimensional bioheat transfer, systemic arterial thermo-fluid dynamics, a thermoregulatory system and clothing is developed to predict body temperature and quantitatively evaluate human thermoregulatory responses. The results show good consistency with the available data, indicating that the present model is capable of accurately predicting human thermal regulation. The inverse problem of predicting comfortable clothing thermal resistance is solved by a bisection searching algorithm. Values for the thermal resistance of comfortable clothing in the human resting state are obtained under different environmental temperatures from -5 degrees C to 20 degrees C. This study is beneficial for the design and selection of clothing (especially functional clothing) and shows potential application in the evaluation of the thermal comfort of building and driving environments. (C) 2016 Elsevier Ltd. All rights reserved.