Abstract: Phenoloxidase (PO) activity was determined in hemocytes and mantle tissues of Manila clamRuditapesphilippinarumwith three shell colors(orange, zebra and white)with shell length of (2.1±0.3)cm, and the hemolymph phenoloxidase activity were also measured in the Manila clam with injection of lipopolysaccharide (LPS) at a dose of 100 μg/mL and peptidoglycan (PGN) at a dose of 20 μg/mL 0, 3, 6, 12, 24, and 48 h after the administration. The results showed that there was significantly higher PO activity in hemocytes than that in mantle in all the three shell-color groups(P<0.05), the maximal level of PO activity in hemocytes of the clam injected with LPS at 3 h in orange, and 12 h in zebra and white clam groups, significant higher in zebra group than that in orange group at 12 h(P<0.05). In the mantle, however, the maximal level of PO activity was observed at 6 h in orange and zebra shell groups and 24 h in white shell color group. The PO activity in hemocytes was found to be declined in orange shell-color clam injected with PGN, the minimal value at 24 h, while the PO activity in hemocytes was clam enhanced in zebra and white color groups,with the maximal level at 12 h in zebra clam and 6 h in white color clam, and significant higher in mantle of zebra color group than that in orange and white color groups(P<0.05). The maximal PO activity in the mantle was detected in the orange color group clam at 12 h after PGN injection, indicating that the responds of PO activity to pathogens are varied with clams with different shell colors, which is involved in close correlation between shell pigmentation and immunity in Manila clam. These findings will provide theoretical support for shell color selection of Manila clam.