The thermal resistance, flow analysis, pressure drop and distribution of coolant inside multilayer LTCC (Low Temperature Co-fired Ceramics) substrate are detailed investigated in this paper. For this reason four various structures of internal channels in the multilayer LTCC substrates were designed and simulated. The simulation 3D model consist of 6 LTCC of DuPont 951® layer with cooling microchannel in middle of substrate, power chips paced on top of LTCC and silver sintered joints under power chips. The impact of the structure of channels, volume flow and power loss of die was simulated, calculated and analyzed by using the simulation software Mentor Graphics FloEFDTM. The structure and size of channels have the significant impact on thermal resistance, pressure of coolant as well as the effectivity of cooling power components which can be placed on LTCC substrate. The thermal resistance was calculated from the temperature gradient among chip junction, the inlet fluid and the thermal load of chip. Optimizing and comparison of cooling channels structure inside LTCC substrates and analyzing the effect of volume flow for achieving the least thermal resistance of LTCC multilayer substrate is the main contribution of this paper.