The raw oils P1, P2, and P3 with different properties from a naphthenic base vacuum residue were used for preparing the mesophase pitch through high-pressure thermal treatment. In the first, H-1 nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy, and vapor pressure osmometry (VPO) were employed to characterize the structural parameters of the raw materials. Development of the anisotropic mesophase was monitored by polarized light optical microscopy. Four n-heptane-soluble (HS), n-heptane-insoluble/toluene-soluble (HI-TS), toluene-insoluble/pyridine-soluble (TI-PS), and pyridine-insoluble (PI) fractions of the product were obtained by extracting with heptane, toluene, and pyridine. The molecular and crystal structure was analyzed by FTIR, H-1 NMR, and X-ray diffraction (XRD). The effects of the feed composition on the formation of the mesophase pitch were investigated. The results showed that the structure of the raw material plays a very important role on mesophase pitch formation. Moreover, the raw material with a higher aromatic, more naphthenic structure and a certain amount of short alkyl side chains was easy to form a mesophase pitch with a larger domain optical texture, lower softening point, and better crystal structure.