Objective Asthma is a chronic immune disease that has become a serious public health problem. The currently available medications are not ideal because of their limitations and side effects; hence, new target proteins and signaling cascades for precise and safe therapy treatment are needed. This work established an ovalbumin-induced asthma rat model and treated it with total flavonoid extract from the Xinjiang chamomile. The proteins that were differentially expressed in the chamomile extract-treated asthmatic rats and the asthma and healthy rat groups were identified using isobaric tagging followed by LC-MS/MS. Kyoto encyclopedia of genes and genomes pathway analysis of the differentially expressed proteins was performed. Results Pathways involved in purine metabolism, herpes simplex infection, and JNK phosphorylation and activation mediated by activated human TAK1 were enriched, indicating the intrinsic links between the mechanism of asthma development and treatment effects. Furthermore, we constructed a protein-protein interaction network and identified KIF3A as a potential target protein of chamomile extract that affected the Hedgehog signaling pathway. Conclusions This study may provide new insights into the pathogenesis of asthma and reveal several proteins and pathways that could be exploited to develop novel treatment approaches.