The aim of this study is to elucidate the toxicity induced by PbCl2, administered in graded doses (1; 2.5; 5 mg/L), in the redox state, in the fatty acid composition and in the histological structure of Mactra corallina digestive glands. Our findings showed a progressive accumulation of Pb in the M. corallina digestive glands in all treated groups. After 5 days of treatment with PbCl2, an increase in H2O2, MDA, PCO, GSH, NPSH and MT levels was observed in the digestive glands of treated groups. Moreover, activities of antioxidant enzymes, such as GPx and CAT, increased while SOD activity decreased in all treated groups, indicating a failure of the antioxidant defense system. Furthermore, the cholinergic function was evaluated by assessing the acetylcholinesterase activity, which was inhibited in all the treated digestive glands compared to the control group. In our experiment, the levels of n-3 (Omega-3) and n-6 (Omega-6) polyunsaturated fatty acids were greatly altered in the groups treated with 5 mg/L of PbCl2 (p < 0.001). Indeed, DHA and EPA decreased significantly in the digestive glands treated with 2.5 and 5 mg/L of PbCl2, respectively. On the other hand, under exposure to the medium and high doses (2.5 and 5 mg/L), arachidonic acid (ARA) and linoleic acid (LA) significantly increased (p < 0.001). These changes in PUFA were confirmed by significant modifications in the polyene and peroxidation indices. The histological findings confirmed the biochemical results.HighlightsIntegrated parameters were used to explore the toxic effect of PbCl2 graded doses in Mactra corallina digestive gland.Metals accumulation in digestive glands of M. corallina was greatly dependent to dose of PbCl2.Metabolic and macromolecules damaging of clams digestive glands were more sensitive at higher PbCl2 doses.Fatty acids composition especially polyunsaturated fatty acids (PUFA) and essentials fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in clams digestive glands were intensively altered at higher PbCl2 doses.Inflammation responses revealed in studied tissue.