The anti-oxidant and immunomodulatory properties of seabuckthorn were studied in vitro using rat spleenocytes and macrophages and in vivo using male albino rats. Addition of chromium or sodium nitroprusside (SNP) to the cells resulted in enhanced cytotoxicity, free radical generation; and decreased glutathione (reduced) levels and glutathione peroxidase activity. Chromium also caused a significant inhibition of both lipopolysaccharide and concanavalin A stimulated lympholcytes proliferation. The alcoholic leaf and fruit extracts of Seabuckthorn at a dose of 500 m g/ml and 1mg/ml respectively inhibited chromium and SNP induced cytotoxicity significantly as determined by acridine orange/ethidium bromide staining and lactate deydrogenase leakage in both lymphocytes and macrophages. These extracts also inhibited chromium and SNP induced free radical production, apoptosis and restored the antioxidant status to that of control cells. The leaf extract itself stimulated lymphocyte proliferation even in the absence of stimulants like concanavalin A and lipopolysaccharide. The extract alone stimulated IL-2 and g -IFN production in the absence of Con A and also inhibited chromium induced decline in IL-2 and g -IFN production, but did not alter IL-4 production. Administration of chromium to male albino rats significantly decreased reduced glutathione (GSH), and increased malondialdehyde, (MDA) and creatine phosphokinase (CPK) levels and enhanced glutamate oxaloacetate transferase (GOT) and glutamate pyruvate transferase (GPT) levels in the serum. Different doses of alcoholic leaf extract of seabuckthorn were evaluated for protection against chromium induced oxidative stress. The results show that the leaf extract at a concentration of 100 and 250 mg/kg bodyweight protected the animals from chromium induced oxidative injury significantly. Administration of leaf extract along with chromium significantly inhibited chromium- induced immunosuppression. The extract did not affect the humoral response but protected the animals from chromium-induced inhibition of DTH response. These observations suggest that the leaf extract of seabuckthorn has significant, cytoprotective and immunomodulatory properties and specifically activates the cell-mediated immune response.