This investigation evaluated the effects of Pb and Hg in Lake Maryout on Clarias gariepinus fish with reference to the effect of meso-2, 3 dimercaptosuccinic acid (DMSA). Fishes divided into Standard group (10 fish) caught from the lake and directly anesthetized to carry out flesh composition and histopathological examination on gills and gonads. An Experimental –group (60 fish) supplied with lake water and divided into sub-group A without treatment, sub-group B, supplied with 5 mg/kg b.w / L of DMSA, sub-group C, supplied with 18 mg/kg b.w/L of DMSA. After 60 days, fish get the same examination as a standard group.   A significant decrease in water content for sub-group B& C, sub-group C with low lipid comparing with sub-group B. Protein levels were significantly increased in both sub-group B&C than sub-group A. The standard gill showed loss of integrity of lamellae and filaments with capillary congestion. Sub-group A showed brachial lesions with the disappearance of the normal architecture. Sub-group B showed middle improved tissues with an organized pillarcellsystem. In sub-group C, filaments had normal architecture with two rows of secondary lamellae perpendicular to each filament. Standard ovaries showed wrinkling pre-vitologenic, vacuolated late pre-vitologenic, and degenerative vitologenic oocyte.  Sub-group A showed few stages of oocytes and wide inter-follicular space. Sub-group B showed some stages of oocytes. Sub-group C showed all stages. Standard testes showed degenerative cellular elements in most seminiferous tubules with dilated congested blood vessels. Sub-group A showed distortion of testicular architecture. Sub-group B showed moderate improvement in testicular pictures. Sub-group C showed organized tubules with all stages. In conclusion, the protective effect of DMSA may be attributed to its activity as a chelating agent with two negatively charged groups that allow it to form complexes with multiple positive charges metal ions as Pb and Hg and reactive oxygen species.