A large-sample-volume constant-flow magic angle sample spinning (CF-MAS) NMR probe is reported for in situ investigating the reaction dynamics, stable intermediates/transition states, and mechanisms of a catalytic reaction. In our approach, the reactants are flowed into the catalyst bed using a fixed tube at one end of the rotor while a second fixed tube linked to a vacuum pump is attached at the other end of the MAS rotor to form a flow inside the catalyst bed by utilizing the pressure difference at both ends of the catalyst bed inside the sample cell space. The formation of the flow through the catalyst bed improves the diffusion of the reactants and products, allowing the use of large sample volume for enhanced sensitivity and thus permitting in situ 13C CF-MAS studies at natural abundance. As an example of application, we show that reactants, products and reaction transition states associated with 2-butanol dehydration reaction over heteropoly acids supported on mesoporous silicalite materials (HPA/meso-silicalite-1) can all be detected in a single 13C CF-MAS NMR spectrum at natural abundance. Coke products can also be detected at natural 13C abundance and under stopped flow condition. Furthermore, we show that the surface functional groups of HPA/meso-silicalite-1 can be identified under the condition of in situ drying using 1H CF-MAS NMR. We also show that the reaction dynamics of 2-butanol dehydration using HPA/meso-silicalite-1 as catalyst can be explored using 1H CF-MAS NMR.