Farfarae Flos (FF) is widely used in china to treat pulmonary disorders such as coughs, bronchitis, tuberculosis and asthmatic disorders. In this study, a ¹H NMR based metabolomic approach coupled with biochemical assay as well as histopathological inspection had been employed to study the protective effect of petroleum extracts of FF (PEFF) against OVA-induced asthma using a rat model. Multivariate analysis revealed that 19 of the perturbed endogenous metabolites in the lung could be reversed by PEFF, and MetPA analysis revealed that the anti-asthamtic effect of PEFF was probably related with regulation of arginine and proline metabolism, pyruvate metabolism and D-glutamine and D-glutamate metabolism. The regulatory effect on the cytokines (IL-4, IL-5, IL-13, and IL-17) and serum HO-1 suggested that the anti-asthmatic action of PEFF was also probably related with the balancing of the Th1/Th2 cells and the Nrf2/HO-1 pathway. The results of chemical analysis showed that the sesquiterpenes were present as the major components in PEFF, and further studies are needed to validate the bioactive compounds responsible for the anti-asthmatic effect of PEFF.