<p>The substructure impact on spindle heating is well known and extensively discussed, and thus many empirical formulas and thermal mechanism models have been established. Nevertheless, the coolant unit role in spindle temperature reduction was not thoroughly characterized. A full and accurate thermal model, especially the thermal assessment resistance with high engineering application value to describe the cooling channel effect, has been still absent so far. For this, this paper integrates the gray-box modeling theory to develop a novel semi-empirical thermal resistance network model of a spindle cooling system with the structural constraint influence considered for the first time. The substructures and its thermal exchange of a cooling passage were first analyzed. A gray-box description for the heat dissipation of a coolant unit was subsequently implemented, and then the thermal resistance theory was introduced to perform the specific modeling tasks. In this process, the thermal equivalent resistance of a rectangular spiral channel was derived based on the formula constructed by Dittus and Boelter, and accordingly the axial and radial heat dissipation resistances of a cooling unit also were formulated separately with the influence of the coolant channel itself and its external structural constraints considered. The effect of cooling channel structure parameters on temperature reduction, meanwhile, was discussed. Next, the lubrication oil film impact wasfactored into the contact heat transfer of bearing ball-raceway, and furthermore the multi-node model of bearings was also revised to correct the double counting on the heat exchanged by oil-air. The thermal network of a motorized spindle was next planned to verify our work, in which both the proposed thermal resistances based on gray-box and axial-radial heat transfer separation for spiral coolant channels and the developed thermal contact transfer model of bearing ball-raceway were employed, and the spindle segmentation factor considering the structural constraint effect also was introduced for modeling simplification. Finally, the above-proposed work was gradually validated experimentally. The temperature simulation based on the latest model, in addition, was added and contrasted with the newly designed grids for further verification. The results indicate that the thermal forecasting is more accurate as the developed gray-box thermal resistance model of a cooling system is applied to assess the spindle heating. And while the influence of lubrication oil film on the contact heat transfer of bearing ball-raceway is integrated, the thermal forecasting error can further be reduced.</p>