Six Ni-Mo catalysts with different metal contents were prepared and characterized by N2 adsorption and X-ray diffractometry. The active phase microstructure of these catalysts was examined by the Raman spectroscopy, temperatureprogrammed reduction(TPR), X-ray photoelectron spectroscopy, and high-resolution transmission electron microscopy. Hydrodesulfurization(HDS) activity of catalyst samples were analyzed in a flow fixed-bed microreactor. The sulfidation degree of Mo and the length of the MoS2 slab slightly increased with the amount of metal loaded following sulfidation. This small change is attributed to polymolybdate species observed in all the oxidized catalysts. Weak metal-support interactions, as determined by the TPR technique, increased the NiSx sulfidation phase and MoS2 slab stacking. The HDS activity of the catalyst samples increased with the number of active sites. For high metal loading catalysts, their HDS activity was nearly identical because the sulfur atoms cannot easily approach active sites. This change is caused by the large number of stacked layers in the MoS2 slabs as well as the decrease in the specific surface area and pore volume of the catalyst samples with an increasing metal loading. Six active materials microstructure of these catalysts was examined by the Raman spectroscopy, temperatureprogrammed reduction (TPR), X-ray photoelectron spectroscopy, and high -resolution transmission electron microscopy. Hydrodesulfurization (HDS) activity of catalyst samples were analyzed in a flow fixed-bed microreactor. The sulfidation degree of Mo and the length of the MoS2 slab slightly increased with the amount of metal loaded following sulfidation. This small change is attributed to polymolybdate species observed in all the oxidized catalysts. Weak metal-support interactions, as determined by the TPR technique, increased the NiSx sulfidation phase and MoS2 slab stacking. The HDS activity of the catalyst samples increased with the number of active sites. For high metal loading catalysts, their HDS activity was nearly identical because the sulfur atoms can not eas ily approach active sites. This change is caused by the large number of stacked layers in the MoS2 slabs as well as the decrease in the specific surface area and pore volume of the catalyst samples with an increasing metal loading.