The present study investigated the effects of stable agonist for prostaglandin (PG) I2 receptor with PGI1 skeleton, SM-10906, on pro-inflammatory cytokine production by mouse peritoneal macrophages (PEMs) in comparison with PGE1 and PGI2. In mouse PEMs, SM-10906 and PGE1 slightly enhanced interleukin (IL)-6 secretion, but had no effects on tumor necrosis factor-alpha (TNF-alpha) or IL-1 production. SM-10906 concentration-dependently inhibited TNF-alpha, IL-1 and IL-6 releases from lipopolysaccharide-activated mouse PEMs, as with PGE1, PGI2 and cAMP analog. Additionally, SM-10906, PGE1 and PGI2 caused concentration-dependent accumulation of cAMP contents in mouse PEMs. It is concluded that PGI1 analog SM-10906 exerts anti-inflammatory effects on stimulated mouse PEMs by increasing in cAMP levels, as with E-series of PG.