The present study was undertaken to evaluate the effects of lansoprazole (LPZ) on lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) signal transduction systems using the 293hTLR4/MD2-CD14 cells. The cells were incubated and then divided into the following groups: (a) untreated group, (b) non-LPZ treated (1h) group, (c) LPZ-treated (1h) plus non LPS-stimulated (1h) group, (d) LPZ-treated (1h) plus non LPS-stimulated (6h) group, (e) LPZ-treated (1h) plus LPS-stimulated (1h) group, (f) LPZ-treated (1h) plus LPS-stimulated (6h) group, (g) non LPZ-treated (1h) plus LPS-stimulated (1h) group and (h) non LPZ-treated (1h) plus LPS-stimulated (6h) group. Samples from each group were subjected to western blotting for analysis of IkB phosphorylation, intranuclear transfer of NF-kB, phosphorylation of MAP kinase (MAPK), intranuclear transfer of interferon regulatory factor 5 (IRF5), and expression of suppressor of cytokine signaling-1 (SOCS1). In the LPZ-treated groups, neither phosphorylation of MAPK nor intranuclear transfer of IRF5 was suppressed under stimulation with LPS, and enhanced intranuclear transfer of NF-kB and increased expression of SOCS1 were noted by comparison with the group treated with LPS alone. These results suggest that LPZ stimulates the expression of SOCS1 and regulates protein phosphorylation through its activity on TLR4 signal transduction under LPS stimulation.