This study was conducted to find out biological response of Manila clam, Ruditapes philippinarum exposed to lead (Pb). Experimental period was four weeks. Experimental groups were composed of one control condition and three lead exposure conditions (0.25, 0.50 and 1.00 mg/l). The results of the study confirmed that lead induces reduction of survival rate and oxygen consumption rate and histopathology of organ structure of the bivalve. Oxygen consumption rate was observed exposure groups lower than control decline by 25%-72%. Histological analysis of organ system illustrated expansion of hemolymph sinus, disappearance of epidermal layer and degeneration of connective tissue layer of the mantle. Also, histological degenerations as epithelial necrosis and hyperplasia of mucous cells are recognized in the gill and it was observed expansion of hemolymph sinus, disruption of epithelial layer, decrease of mucous cell and degeneration of connective tissue layer in the foot. In the digestive diverticulum, it was showed atrophy of basophilic cell and degeneration of epithelial cell in the digestive tubules, and as the concentration of lead increased the accumulation of lipofuscin increased.