Qing-Wen-Jie-Re mixture (QWJR) has been used in the treatment of the coronavirus disease 2019 (COVID-19) in China. However, the protective mechanisms of QWJR on viral pneumonia remain unclear. In the present study, we first investigated the therapeutic effects of QWJR on a rat viral pneumonia model established by using polyinosinic-polycytidylic acid (poly (I:C)). The results indicated that QWJR could relieve the destruction of alveolar-capillary barrier in viral pneumonia rats, as represented by the decreased wet/dry weight (W/D) ratio in lung, total cell count and total protein concentration in bronchoalveolar lavage fluid (BALF). Besides, QWJR could also down-regulate the expression of inflammatory factors such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6. More M1-type macrophage polarization was detected by calculating CD86+ cells and CD206+ cells and validated by the decline of inducible nitric oxide synthase (iNOS) and elevated arginase-1 (Arg-1) in lung. Finally, serum untargeted metabolomics analysis demonstrated that QWJR might take effect through regulating arginine metabolism, arachidonic acid (AA) metabolism, tricarboxylic acid (TCA) cycle, nicotinate and nicotinamide metabolism processes.