OBJECTIVE: To investigate the property, skin irritation and in vitro transdermal absorption of Diclofenac sodium microemulsion (DS-ME), and to explore the feasibility of local external use of it. METHODS: The content of DS in DS-ME was determined by ultraviolet spectrophotometry. The distribution of particle size was determined by laser particle size analyzer. The effects of DS-ME and blank micro-emulsion on normal skin of single administration, normal skin of multiple administration and damaged skin of single administration were investigated by rabbit skin irritation test. The transdermal parameters of DS-ME and commercially available DS gel through isolated skin of mice were compared by Franz diffusion cell. RESULTS: The prepared DS-ME was O/W microemulsion with particle size of (30.140±9.020) nm. Compared with blank ME, DS-ME had no significant difference in rabbit skin irritation score. Steady permeation rates of DS-ME and commercially available DS gel were 34.16 and 18.62 μg/(cm2·h), respectively; the permeation coefficient of them were 1.029 and 0.561 cm/h; the delay time were 0.124 2 and 0.367 2 h. CONCLUSIONS: The particle size of DS-ME is small and not irritant to skin, and can improve transdermal absorption rate of DS.