Objective To investigate the effect and anti-inflammatory mechanism of astragalus pratensison expression of lacrimal gland related inflammatory factors and NF-κB signaling pathway in experimental dry eye disease rats. Methods In this study, 35 adult healthy male rats were randomly divided into 5 groups: blank control group(N), model control group(M), solvent control group(R), positive drug control group(Y), and astragalus pratensis administration group(T), with 7 rats in each group. The N group does not do any processing. Experimental dry eye models were constructed in groups M, R, Y and T, and drug administration was started in groups on the first day of modeling, and the administration cycle was 14 days. Fluorescein staining(FL), break-up time(BUT) and tear secretion Schirmer I-test(SIT) were evaluated. The levels of TNF-α, IL-1α and IL-6 in serum of rats in each group were detected by ELISA, and the expression of major factors of NF-κB signaling pathway(IKK-α, IKK-β, Iκ-B, NF-κB-P65) in lacrimal tissues of rats in each group were detected by immunohistochemistry and PCR to investigate the expression of lacrimal gland related inflammatory factors and pathways in rat. Results FL, BUT and SIT showed that astragalus pratensis can improve tear secretion and prolong corneal rupture time in rats with dry eye disease. ELISA results showed that astragalus pratensis could decrease the expression levels of TNF-α, IL-1α and IL-6 in the serum of rats with dry eye disease. Immunohistochemical and PCR assay results showed that astragalus pratensis could reduce the expression level of major factor of NF-κB signaling pathway. Conclusion Astragalus pratensis can reduce the expression of lacrimal inflammatory factors by inhibiting NF-κB signaling pathway, and play a role in alleviating the inflammatory reaction of lacrimal gland in rats with dry eye disease.