AIM: To investigate the effect of morroniside (Mor) on lipopolysaccharide (LPS)-treated iris pigment epithelial cells (IPE). METHODS: IPE cells were induced by LPS and treated with Mor. Cell proliferation was detected by cell counting kit (CCK) -8, apoptosis was detected by flow cytometry, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA) kits, and the protein expression of TLR4, JAK2, p-JAK2, STAT3, and p-STAT3 was analyzed by Western blotting. In addition, overexpression of TLR4 and Mor treatment of LPS-stimulated IPE cells were also tested for the above indices. RESULTS: Mor effectively promoted the proliferation and inhibited the apoptosis of LPS-treated IPE cells. In addition, Mor significantly reduced the levels of TNF-α, IL-6, and IL-8 and significantly inhibited the expression of TLR4, p-JAK2, and p-STAT3 in LPS-treated IPE cells. The effect of Mor on LPS-treated IPE cells was markedly attenuated after overexpression of TLR4. CONCLUSION: These findings suggest that Mor may ameliorate LPS-induced inflammatory damage and apoptosis in IPE through inhibition of TLR4/JAK2/STAT3 pathway.