Objective and Design: This study investigated the role of the prostaglandin E receptor EP3 subtype in the development of inflammatory synovitis.¶Materials and Methods: We examined the EP3 mRNA expression in the synovial tissue of rats with adjuvant arthritis and the effect of selective EP agonists on IL-6 production by cultured rat synovial cells.¶Results: Of the two rat EP3 isoforms, rEP3B mRNA but not rEP3A mRNA was expressed in rat synovial cells. RT-PCR and ELISA were used to analyze the effects of selective EP3 agonist (ONO-AE-248) on IL-6 production by rat cultured synovial cells. This selective EP3 agonist induced IL-6 production by rat synovial cells in a time- and dose-dependent manner.¶Conclusions: Our results suggest that PGE2 upregulates IL-6 production by synovial macrophages and fibroblasts through rEP3B in rats with adjuvant arthritis.¶