Myriads of research reviews have justified that unrestricted and uncontrolled exposure to heavy metal contamination through occupation and environmental pollution generally result in health risks with attendant health burdens including genetic birth defects. This study evaluates the anticlastogenic potential of Euphorbia heterophylla leaf extract against lead-induced polychromatic erythrocytes and the damaged tissues of the albino rats. A total of sixty (60) albino rats were segregated into three sets namely Set I, II and III. Each set contains twenty albino rats which were then divided into four groups A, B, C and D containing five rats each. Group A serves as control and were treated with distilled water only. Group B rats received 2.5 mg/kg lead acetate while group C rats were simultaneously fed 25, 50 and 100 mg/kg Euphorbia heterophylla leaf extract concentrations and 2.5 mg/kg lead acetate at ratio 1:1. Rats in group D were administered 25, 50, and 100 mg/kg Euphorbia heterophylla leaf extract. The schedule of the animal treatment was divided into three set I, II and III while micronucleus assay and histopathological examination were carried out on the test animals. Results show that polychromatic erythrocytes induced by lead acetate was significantly (P<0.05) reduced in group C animals (6%), while lead acetate administered to animals in group B was highly clastogenic. Besides, the histopathological architecture of the rat tissues indicates protection offered by the extract against tissue atrophy.