Pathological pigmentation usually occurs under the conditions of trauma, surgery, sunshine, etc. The clinical preferred method is laser treatment. Although the curative effect is significant, there is recurrence of pigmentation, under which the specific mechanism remains unclear. In this study, for the first time, the adult zebrafish was used to establish a laser ablation animal model. The results showed that pigments in zebrafish skin reappeared after laser ablation. And the gray value, area and distribution of reappeared pigments were highly related to energy density and pulse time of the irradiated laser. It is found that pigments area reduction was most significant on the first and second days after laser ablation, and recurrence effect become worst on the fifth day; The high energy density group was not as good as the low energy density group in the freckle effect, and pigmentation recurrence of the latter was not significant; The protein level of macrophage migration inhibitory factor(MIF)in laser ablation recurrence site was upregulated and positively correlated with the degree of recurrence of pigmentation. MIF has a strong promoting effect on angiogenesis, so recurrence of pigmentation might be induced by up-r
egulation of MIF. The above results suggest that the freckle effect of Ps lasers is significantly better than that of NS lasers. Lowenergy laser combined with MIF regulation may help to inhibit angiogenesis after laser ablation, thereby reducing pigment recurrence, which provides direct theoretical guidance for clinical application of laser ablation.