The thermal reaction of Karamay residue was carried out in a micro batch reactor under nitrogen atmosphere. The oil was taken out through an online sampling tube. The asphaltene and coke contents of cracked residue at different reaction times were determined. The phase separation of residue oil was observed by an optical microscope, and the colloidal stability of residue oil was determined quantitatively by the mass fraction normalized conductivity method. The alkyl side chain length of resins and asphaltenes was analyzed by infrared spectroscopy, and their structure parameters were calculated via density method. The macroscopic phenomena of phase separation, coke formation and colloidal stability deterioration were correlated with micro molecular structure. The results showed that the increase of asphaltene condensation degree and the decrease of peptizing ability of resins were the essential reasons for phase separation and coking during thermal reaction. At the initial coke formation point, the condensation degree of resins and asphaltenes during low temperature reaction was lower than that of high temperature reaction.