Phycoerythrin from the red alga Porphyra yezoensis has been demonstrated to possess antioxidative activity and is expected to have anti-inflammatory activity. In this study, we examined the effects of phycoerythrin and its pigment moiety, phycoerythrobilin, on the degranulation of mast cells. Phycoerythrin (0.01 mg/mL) and phycoerythrobilin (1 μmol/L) significantly inhibited calcium ionophore (A23187) induced release of β-hexosaminidase from rat basophilic leukemia (RBL-2H3) cells (approximately 50% and 40%, respectively). Phycoerythrobilin significantly suppressed IgE-antigen-stimulated degranulation of RBL-2H3 cells, while phycoerythrin had no effect. A23187-induced degranulation of peritoneal exudate cells (PEC) prepared from rats treated orally with phycoerythrin (4 mg/kg) or phycoerythrobilin (1 μmol/kg) was significantly reduced compared to control PEC. These results suggest that phycoerythrin and phycoerythrobilin exhibit anti-inflammatory activities through the suppression of mast cells degranulation in vivo.