In cardiovascular diseases, endothelin type B (ET B ) receptors in arterial smooth muscle cells are upregulated. The present study revealed that organ culture of rat mesenteric artery segments enhanced endothelin ET B receptor-mediated contraction paralleled with increase in the receptor mRNA and protein expressions. The endothelin ET B receptor-mediated contraction was associated with increase in phosphorylation of extracellular regulation kinase 1 and 2 (ERK1/2) proteins and elevated levels of intracellular calcium. The elevation curve of intracellular calcium consisted of two phases: one rapid and one sustained. Inhibition of ERK1/2 phosphorylation by SB386023 or blockage of calcium channels by nifedipine significantly reduced the endothelin ET B receptor-mediated contraction (P<0.05) and decreased the sustained phase of intracellular calcium level, but not the rapid phase. Thus, phosphorylation of ERK1/2 proteins and elevation of intracellular calcium level are required for endothelin ET B receptor-mediated contraction in rat mesenteric artery.