Because of its complexity and inferior quality, it is difficult to understand the structure and reactivity of heavy oil. In this paper, we combined the eight group-fraction chromatographic separation method, the modified Brown-Ladner (B-L) method, and the pyrolysis gas chromatography mass spectrometry (Py-GC/MS) analytical method to offer a convenient and efficient method to systematically understanding the average structure, the alkyl side chain length distribution, and the reactivity of Iranian vacuum residue (VR). The results showed that VR can be divided into eight group-fractions (saturate, light aromatic, middle aromatic, heavy aromatic, light resin, middle resin, heavy resin, and asphaltene), which could well reflect the difference of their compositions and structures. Investigating the reactivity of eight group-fractions is valuable for understanding the reactivity of VR in depth. The coking tendency of eight group-fractions are significantly increased from saturate to asphaltene, which are in accordance with their size of aromatic nucleus. But their trackable molecular constituents detected by Py-GC/MS are similar. The proposed average molecular structural model based on the modified BL method and Py-GC/MS analytical results could reflect the structure and reactivity of VR and its subfractions intuitively.