Abstract: Tripterygium wilfordii is a very excellent Chinese medicine for the treatment of Rheumatoid arthritis (RA), while its clinical applications are confined by its severe side effects. Previous investigation indicated that roasting processing in an oven at 200 ℃ can not only significantly reduce the toxicity but also enhance the therapeutic efficacy of Tripterygium Wilfordii. In order to disclose the rationality of roasting processing, improve the safety and effectiveness of Tripterygium wilfordii in clinical application and obtain excellent anti-inflammatory leader compounds, the UPLC-Q-TOF MS method was used to analyze the two groups, which were untreated and processed Tripterygium wilfordii groups. Data were processed by principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) to find the difference between two groups. The accurate m/z values of Q-TOF MS, MS² fragments were applied to constituent identification. The results indicated that 81 constituents had significant differences between two groups. The structures of 35 compounds were identified, of which the contents of 26 constituents including celastrol and celafurine were decreasing, while the contents of 7 constituents including 1-desacetylwilfordine were increasing, meanwhile two new components were occurring. Of the 81 components, alkaloids accounted for 69%, and triterpenes accounted for 12%. The result indicated that celastrol and many alkaloids significantly changed after processing, which were primary active and toxic components of Tripterygium wilfordii. The results indicated that thermal changes of alkaloids and celastrol probably play an important role in the toxicity reducing and efficacy enhancing of Tripterygium wilfordii under roasting processing.