Abstract: In this study, the toxic and mutagenic effects of Euphorbia schimperiana-methanol extract were investigated in Swiss albino mice of both sexes. In the course of a toxicological evaluation of this extract and prior to field applications, selected acute toxicity tests (oral, dermal, skin and eye irritation) were firstly determined. Then, three doses of acute oral (maximum, half maximum and double maximum) were chosen for the assessment of mutagenicity using the micronucleus test. While, the tested extract was slightly toxic non, irritant to the skin and moderately irritant to the ocular tissue it significantly increased the frequency of micro-nuclei particularly at the doubly maximum dose in both sexes. In conclusion, the results indicated that the Euphorbia schimperiana-methanol extract has slightly toxic effect. But has a potent mutagenic effect in mice.