OBJECTIVE： To prepare Melatonin solid lipid nanoparticles （MT-SLNs）， and to investigate in vitro transcutaneous absorption characteristics of them in isolated skin of mice. METHODS： Using melatonin （MT） as model drug， glycerin sorbate as oil phase， poloxamer 188 （F188） as emulsifier， MT-SLNs was prepared by melt-emulsion method. The morphology of MT-SLNs was observed by TEM； the particle size distribution of MT-SLNs was measured by laser particle size analyzer， and the infrared spectrum characteristics were measured by infrared spectroscopy. The entrapped efficiency and drug loading amount were determined by HPLC and ultrafiltration centrifugation method. The transcutaneous absorption characteristics in vitro of MT-SLNs and MT raw material were compared using Franz diffusion cells method. RESULTS： The formulation of MT-SLNs included 2.5 mg/mL MT raw material， 25 mg/mL glycerin sorbate and 1％F188. The obtained MT-SLNs were spherical， and no aggregation was observed. Average particle size was （67.88±0.17）nm， and polydispersity index was 0.188±0.001. The characteristic absorption peaks of N—H stretching and bending vibration were not found in infrared spectra， and the characteristic absorption peaks of C—H stretching vibration of benzene ring shifted red to 1 750 cm－1. The entrapped efficiency and drug loading amount of MT-SLNs were （87.54±5.31）％ and （8.42±0.78）％. The transcutaneous absorption behavior of MT-SLNs and MT raw material conformed to zero-order kinetics release rule. The steady-state transmission rate of MT-SLNs [（31.71+2.78） μg/（h·cm2）] was significantly higher than that of its raw material [（10.32±3.24） μg/（h·cm2）]， and its lag time [（0.17±0.01） h] was significantly shorter than that of its raw material [（1.57±0.37） h] （P＜0.01）. CONCLUSIONS： Prepared MT-SLNs have small particle size and distributed evenly， and can promote in vitro transcutaneous absorption.