Food-grade carboxymethyl cellulose was prepared from maize husk agro-waste and was evaluated sub-chronic oral toxicity in Swiss albino mice. 40 male mice were divided into 4 groups and fed diets with 0 (control) - 10% CMC for a period of 3 months. Daily oral doses were 5 - 20mg/g body weight to the mice/day. Animal care and handling were conformed according to internationally accepted standard guidelines. Haematological and biochemical parameters were monitored during this period. At the end of the study, tissues and organs were studied for histopathological changes. Repeat-dose oral toxicity study was carried out according to OECD guideline 408. The result did not show any treatment related abnormalities in terms of haematological and biochemical parameters. However, water intake, urine production and urinary sodium excretion increased with increasing doses of CMC. The weekly body weight showed no significant differences between control and mice treated with different doses of CMC. In mice of the treated groups, no abnormalities in the histopathology of liver, heart, lung and kidney were detected. This indicated the prepared CMC has no toxic effect at different doses on cellular structure, and support the safety use of CMC as food additives and an excipient for pharmaceuticals.