摘要： Port wine stains (PWSs) are congenital vascular malformations that progressively darken and thicken with age. Currently, laser therapy is the most effective way in clinical management of PWS. It is known that skin pigmentation (melanin content) affects the radiant exposure that can be safely applied to treat PWS. However, the effect of melanin distribution in the epidermis on the maximum safe radiant exposure has not been studied previously. In this study, 10 different morphological distributions of melanin were proposed according to the formation and migration characteristics of melanin, and the two-scale heat transfer model was employed to investigate the influence of melanin distribution on the threshold radiant exposure of epidermis and blood vessels. The results show that melanin distributions do have a strong effect on laser parameter selection. When uniform melanin distribution is assumed, the threshold radiant exposure to damage a typical PWS blood vessel (50 μm diameter) is 8.62 J/cm2 lower than that to injure epidermis. The optimal pulse duration is 1–5 ms for a typical PWS blood vessel of 50 μm when melanin distribution is taken into consideration. PWS blood vessels covered by non-uniformly distributed melanin are more likely to have poor response to laser treatment.