A B S T R A C TThe histo and clinicopathological effect of MonoSodium Glutamate (food enhancer) and Sodium MetaBisulfite (food preservatives) on different tissues and organs of male Albino rats were investigated. Eighty male Albino rats (150-180 gm) were divided into 5 groups: control group and 4 groups administrated 30 and 60 mg MSG /kg b.wt; 260 and 520 mg SMB /kg b.wt for 12 weeks per os. Rats were sacrificed at 2, 4, 8 and 12 weeks from beginning the experiment. Significant decrease in Hb concentration, PCV, MCV and MCH; and significant increase in RBCs, leukogram, platelet counts, GPT, GOT, BUN, creatinine and total protein were observed in rats administred 30 and 60 mg MSG /kg b.wt. Histopathologically, mild changes were observed in liver, kidney, heart, stomach and intestine. Multifocally, marked degenerative and necrotic changes were seen in the lining epithelium of the seminiferous tubules and neurons particularly in high doses after 8 and 12 weeks post MSG administration. On the other hand, administration of SMB by a dose 260 and 520 mg/kg b.wt resulted in significant increase in Hb, MCH, MCHC, Platelets, total leukocytic counts, GPT, GOT, albumin, BUN and creatinine values. Microscopically, hyperplasia of the biliary epithelium, lymphoid depletion of white pulpe of the spleen and mild degenerative changes in the lining epithelium of the seminiferous tubules, neurons and cardiac muscle were detected. Moderate changes were seen in the renal tissue characterized by degenerative changes in the endothelial cells of glomeruli and renal tubular epithelium with desquamation of the lining epithelial cells and presence of hyaline casts in the lumen. Multifocally, necrotic gastroenteritis with heavy leukocytic infiltration in the lamina propria of the stomach and intestine. In conclusion, the addition of MSG resulted in marked changes in brain and testes while, SMB lead to marked changes in gastrointestinal tract and brain. These changes are dose and time independent in MSG and dose independent only in SMB.