Vasodilating actions of sinomenine were examined using rat aorta ring strips. Sinomenine (0.1 to 100 μM) dilated norepinephrine (NE, 5 μM)-induced vasoconstriction in a concentration-dependent manner reaching 68.8±5.1% (n=6, P<0.01) at a concentration of 100 μM. Sinomenine (100 μM) also attenuated KCl (60 mM) and phorbol 12, 13-dibutyrate (PDB, a protein kinase C, PK-C, activator, 300 nM)-induced vasoconstriction by 86.9±8.5% (n=6, P<0.01) and 49.9±9.8% (n=6, P<0.01), respectively. Pretreatment with nicardipine (a Ca2+ channel antagonist), staurosporine (a PK-C inhibitor), NG-monomethyl-L-arginine acetate (L-NMMA, a nitric oxide, NO, synthesis inhibitor), and indomethacin (a cyclooxygenase inhibitor) were carried out. Nicardipine (0.1 μM) led to a significant decrease in the vasodilating potential of sinomenine (at 100 μM, 68.8±5.1% vs. 35.5±6.9%; n=5, P<0.001). Pretreatment with staurosporine (30 nM) reduced sinomenine-associated vasodilation from 68.8±5.1% to 49.5±7.7% (n=5, P<0.001), and L-NMMA (100 μM) and indomethacin (10 μM), to 25.3±2.3% (n=5, P<0.001) and to 37.1±9.3% (n=5, P<0.001), respectively. The responses were almost similar to the results without endothelium. Therefore, these results indicate that sinomenine causes the vasorelaxation by the mechanisms involved with the inhibitions of Ca2+ channel and PK-C activity, and also with the activations of NO and prostaglandin (PG) I2 syntheses in endothelium.