Background: This investigation aimed to evaluate the therapeutic impact of the Yigan Xiaozheng formula on liver cirrhosis in rats, particularly induced by diethylnitrosamine (DEN). The study focused on analyzing liver structure, cell apoptosis, and the modulation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway, employing a combination of network pharmacology and experimental approaches. Methods: A DEN-induced rat model of liver cirrhosis was established to assess the formula's effectiveness. Parameters such as overall health, liver morphology, and survival were monitored. Network pharmacology was employed to decipher the active compounds and key targets of the formula in addressing liver cirrhosis. Predictions made via network pharmacology were substantiated through experimental validation in the animal model. Results: Administration of the Yigan Xiaozheng formula led to noticeable improvements in clinical symptoms of liver cirrhosis in rats, marked by enhanced body weight, lessened liver pathology, and higher survival rates. Network pharmacological analysis unveiled intricate interactions between active ingredients of the formula and cirrhosis-related targets. Protein-protein interaction (PPI) networks pinpointed crucial proteins and regulatory modules. Enrichment analysis underscored a significant involvement of the JAK2/STAT3 signaling pathway. On a molecular scale, the formula was observed to reduce the expression of BCL-2 associated X protein (Bax) and cytochrome C (Cyt-C), diminish the Bax/B-cell lymphoma 2 (Bcl-2) ratio, and impede JAK2/STAT3 pathway activation, thereby curtailing liver fibrosis and cellular apoptosis. Conclusion: The study demonstrates the Yigan Xiaozheng formula's capacity to ameliorate liver cirrhosis in a DEN-induced model, primarily through its active ingredients' interactions with cirrhosis targets and modulation of the JAK2/STAT3 pathway. These findings endorse the potential of this traditional Chinese medicinal formula as a viable treatment option for liver cirrhosis.