AIM:This study investigate the mechanism of action of Qingxuan Runmu Yin(QRY) in the treatment of dry eye based on transcriptomics and network pharmacology approaches. Further,the mice model of dry eye was employed to validate the efficacy and key targets of the QRY. METHODS:Using RNA-seq technology to detect differentially expressed genes (DEGs) between mice in the dry eye group and mice in the normal group, we screened the active ingredients and potential targets of QRY through the TCMSP and TCMIP databases, and then overlapped the two targets to obtain the key targets and then carried out the GO function and KEGG enrichment analysis , so as to build a network of "Drug-Component-Target-Signalling Pathway protein-protein interaction(PPI); mice were examined for SIT, BUT, and FL every 7 days from the beginning of the animal experiments; HE staining was performed to observe pathological changes in mouse corneal tissues; Elisa, Western blot and qRT-PCR were performed to verify the mRNA and protein expression levels of the core targets in mouse corneal tissues. RESULTS:2234 DEGs in dry eye mice and normal mice, 233 active ingredients and 457 related targets of QRY, a total of 64 overlapping targets were obtained, the results of the analysis of the GO function and KEGG pathway showed that they were closely related to the inflammatory , and core targets such as IL-1β, IL-6, and TNF were screened by PPI network construction; the results of SIT, BUT and FL in the QRY group were statistically significant compared with those in the model group (p <0.05), the results of HE staining showed that the corneal epithelial cell stratification was disordered and the corneal morphology was changed in the dry eye model group, while QRY group could effectively improve the corneal roughness and stratification disorder, and the morphology was close to that of the blank group after the treatment; the results of Elisa, Western blot and qRT-PCR showed that the RNA levels of IL-1β, IL-6, and TNF-α in the QRY group and the protein expression showed a similar decreasing trend compared with that of the model group. CONCLUSIONS:The results indicate that QRY works through the combination of multi-components, multi-targets and multi-pathways, and uses quercetin and other main components to regulate the core targets such as IL-1β, IL-6, TNF and so on, thus inhibiting the AGE-RAGE/TNF/IL-17 signalling pathway to achieve effective treatment of dry eye.