Epigallocatechin gallate (EGCG) is the major polyphenol in green tea and the main bioactivecompound responsible for the health benefits of tea consumption. The molecule exhibits antimicrobialand anti-inflammatory activities. However, little is known about the molecular mechanismsby which EGCG elicits those activities. In this study, we examined the effects of EGCG onlipopolysaccharide (LPS) endocytosis and LPS-induced NO production. We also investigated themechanism with focus on the effect of EGCG on interaction between small GTPase Rab5 and caveolin-1. EGCG suppressed endocytosis of LPS and LPS-induced nitric oxide production inmouse macrophage-like cells (RAW 264). EGCG suppressed the Rab5-caveolin-1 interaction andreduced Rab5 activity. The results suggest that EGCG reduced LPS-induced innate immune responsesthrough suppression of LPS endocytosis by interfering with Rab5-caveolin-1 interactionand by reducing Rab5 activity.