Objective：To study the influence of agouti signal protein （ASIP） on melanocyte function in skin autograft, so as to understand the cause of hyperpigmentation in skin autograft. Methods： Guinea pigs were used to establish a skin autograft hyperpigmentation model. The skin autografts in model animals were injected with ASIP or normal saline （control）. RT-PCR technique was used to detect the tyrosinase mRNA expression in melanocytes of skin autografts and Masson-Fontana staining technique was used to detect the melanin contents in skin autografts in ASIP treatment group; and the results were compared with those of control group （n= 13） and normal guinea pigs （n= 5）. Results： The expression of tyrosinase mRNA and the melanin content in skin autografts in ASIP treatment group were both lower than those of control group and normal guinea pigs （P〈 0.01）. Conclusion： The results indicate that ASIP can antagonize the melanogenic effect of α-MSH, resulting in reduced pigmentation in skin autografts. It is also indicated that overexpression of α-MSH in epidermal cells after skin grafting is an important cause of hyperpigmentation in skin autografts