Abstract : Kappaphycus alverazii is commonly cultured in Vietnam and mainly contains carrageenan that is useful in food, beverages, functional food, and pharmaceuticals. The study focused on the evaluation for the semi-chronic toxicity of carrageenan on guinea pig (Cavia porcellus) for 42 days, inside, 21 first days (experiment), and 21 next days (recovery). Carrageenan extracting from Kappaphycus alverazii by the enzyme-assisted method and the purification of carrageenan by using 96 % ethanol. Mice were observed on clinical, weighed, evaluated on the chemical composition of urine and blood, and sliced cells (liver, kidney, and spleen). The results showed that carrageenan extracting by the enzyme-assisted method and purifying by 96 % ethanol was non-toxicity. Carrageenan did not impact the liver, kidney, and spleen of experimental mice, exhibited on the microscopy figure. The fresh weight of the liver, kidney, and spleen increased according to adulthood time, suitable for the weighing increase of mice. The chemical composition of urine and blood was a non-significant difference between mice groups drinking carrageenan and the control group, except for mononuclear leukocyte (M) (MPV) (p<0.05).