Ten different morphological distributions of melanin were proposed according to their formation and migration characteristics, and the two-scale skin model was applied to investigate the influence of melanin distribution, pulse duration, diameter and depth of pathological vessels on the radiant exposure thresholds of epidermis and blood vessels during the laser therapy of Port Wine Stains. The results show that distribution of melanin has a greater influence on the epidermal radiant exposure threshold, but has no obvious effect on that of blood vessels. It is conducive to cure vascular skin diseases with more uniform distribution of melanin, smaller and shallower blood vessels. Spray duration should be prolonged when melanin only distributes in the basal layer of epidermis. With optimized curative effect for vascular skin diseases, long laser pulse (15-20 ms) will be a good choice for more uniform distribution of melanin and larger blood vessels, which is close to the thermal relaxation time of pathological vessels. Shoter pulse (<5 ms) should be chosen for smaller and deeper vessels.