Sodium thiosulfate (STS), a cyanide antidote has been reported to possess antioxidant and calcium chelation effects, useful for the treatment of renal failure due to vascular calcification and urolithiasis. The present study investigated the in vivo modulatory effects of STS on erythrocyte calcium, phosphorous levels, lipid peroxidation, antioxidant enzyme and membrane ATPase activities (Ca, NaK, Mg and 5'' nucleotidase) in an adenine induced model of vascular calcification in rats. Adenine (0.75%) was supplemented through the diet for 28 days, which resulted in significantly ( < 0.05) increased circulating calcium and phosphorous product and oxidative stress within the RBCs, as measured from lipid peroxidation and reduced antioxidant enzymes. The membrane ATPase activities were altered (increased Ca, NaK ATPase and decreased Mg ATPase, 5' nucleotidase) compared to the rats fed on normal diet. STS (400 mg/kg) given orally was effective in establishing a normalcy in the RBC alterations. This effect was more pronounced, when STS was given from day 28 to day 49 after induction of calcification, instead of day 0 to day 28. These findings may benefit to evaluate the effectiveness of STS therapy in patients with chronic renal failure associated with increased circulating calcium and phosphorous product that leads to stiffening of vascular smooth muscles of aorta, due to calcium deposition.