OBJECTIVE: To prepare zolmitriptan-diclofenac microemulsion, and conduct quality evaluation and in vitro transdermal study. METHODS: Using solubility and microemulsion area in pseudo-ternary phase diagram as indexes, the types of oil phase and mixed emulsifier ratio of zolmitriptan-diclofenac microemulsion were screened; the microemulsion quality was inspected using particle size, Zeta potential, appearance and stability. HPLC was used to measure the contents of zolmitriptan and diclofenac. Transdermal diffusion test instrument was used, 2 g microemulsion was smeared in cuticle of extracouporeal rats’ skin, and cumulative transdermal rate in 24 h was determined. RESULTS: The microemulsion formulation was as follow as 10% oil phase (octanoic acid triglyceride), 25% mixture emulgator [polysorbate 80-brij 97 (1 ∶ 1)], 8.3% propylene glycol and 25 mg zolmitriptan, 1.25 mg diclofenac, and water adding to 100 mL. The average particle size of prepared microemulsion was (28.2±2.5) nm, Zeta potential was (-3.25±0.33) mV, the appearance was rounding; the microemulsion showed no stratification or flocculation at room temperature after placed for 1 month. Contents of zolmitriptan and diclofenac were 0.248 mg/mL, 12.46 mg/mL (n=3); 24 h cumulative transdermal rates were 80%, 75%. CONCLUSIONS: Zolmitriptan-diclofenac microemulsion is prepared, and its in vitro transdermal ability is good.