Abstract：This paper discussed and analyzed the principles，methods，formulas，and medicinals in Wen Yi Lun (Treatise on Pestilence). The analysis found that Wen Yi Lun ， the earliest monograph on treating pestilence，contains a complete set of principles，methods，formulas，and medicines that WU Youke used in the syndrome differentiation and treatment of pestilence，with many innovative ideas. Also， WU Youke proposed two new etiological theories，namely pathogenic qi theory and pestilent qi theory， which insisted that pestilence is different from cold damage. WU Youke also established a model of exterior-interior syndrome differentiation and created a system of syndrome differentiation based on nine kinds of exterior-interior disease locations and their corresponding manifestations. The theory of depressed yang transforming into heat was put forward and elucidated，which reveals that the basic pathogenesis of pestilence is the pathogen obstructing qi movement，depressed yang transforming into heat or fire，qi consumption of qi and blood，and damage to liquid and fluid. The treatment emphasizes that dispelling pathogen is the first，which is，to locate the pathogen and find out the development trend of pathogen， and then to make good use of the methods of sweat promotion， emetic promotion， and purgation promotion for expelling pathogen and restoring the normal qi movement. Besides， he enriched the formulas and medication of offensive purgative method and the treatment of pestilence. The theory of depressed yang transforming into heat is the core of academic ideas of WU Youke and the guidance of specific applications of syndrome differentiation， treatment methods， formulas and medication， and contraindications to the treatment of pestilence.