Laser speckle contrast imaging (LSCI) is a powerful tool to monitor blood flow distribution and has been widely used in studies of microcirculation, both for animal and clinical applications. Conventionally, LSCI usually works on reflective-detected mode. However, it could provide promising temporal and spatial resolution for in vivo applications only with the assistance of various tissue windows, otherwise, the overlarge superficial static speckle would extremely limit its contrast and resolution. Here, we systematically investigated the capability of transmissive-detected LSCI (TR-LSCI) for blood flow monitoring in thick tissue. Using Monte Carlo simulation, we theoretically compared the performance of transmissive and reflective detection. It was found that the reflective-detected mode was better when the target layer was at the very surface, but the imaging quality would rapidly decrease with imaging depth, while the transmissive-detected mode could obtain a much stronger signal-to-background ratio (SBR) for thick tissue. We further proved by tissue phantom, animal, and human experiments that in a certain thickness of tissue, TR-LSCI showed remarkably better performance for thick-tissue imaging, and the imaging quality would be further improved if the use of longer wavelengths of near-infrared light. Therefore, both theoretical and experimental results demonstrate that TR-LSCI is capable of obtaining thick-tissue blood flow information and holds great potential in the field of microcirculation research.