Abstract: To investigate lead adsorption effects of Sepia ink melanin in vitro and in vivo,the melanin was obtained by using three extraction methods(water washing,pickling and alkaline protease hydrolysis.),and the preparation method was determined based on lead adsorption capacity in vitro. Then the better one was characterized by scanning electron microscope and Fourier transform-infrared spectroscopy to analyze the physical and functional groups. The experimental model of lead-poisoning mice was established by drinking lead acetate solution. Weight,liver index and the lead content in liver and blood of mice were respectively determined. The adsorption effect of melanin in vivo was analyzed,and the pathological changes of liver were observed by hematoxylin-eosin staining. Results showed that the Sepia ink melanin from alkaline protease hydrolysis was better than the other two methods,of which the adsorption capacity reached(256.06±14.12)mg/g. SEM and FT-IR confirmed that the adsorption reaction mainly existed on the surface of the melanin and the major functional groups involved in adsorption reaction were-OH,-NH,-COOH. Middle and high dose of melanin groups had a significant effect of absorbing lead in liver and blood(p<0.01),declined 17.18%±0.76% and 31.09%±2.48%,20.85%±0.96% and 34.45%±3.31% respectively. Hematoxylin-eosin staining showed that melanin had the relation of liver repairing. The present study suggested that melanin with the process of alkaline protease hydrolysis had good effect of lead absorption capacity,which would have an application prospect of adsorption material.