Abstract: OBJECTIVE To prepare llidocaine gel-microemulsion, and study the pharmacodynamic effects of llidocaine gel-microemulsion. METHODS To use ethylis oleate as oil phase, Polysorbate 80 as surfactant, ethanol as cosurfactant, we prepared lidocaine microemulsion by water titration method. With Carbopol 940 as a substrate, we prepared microemulsion-based gel of lidocaine by direct swelling method. To measure particle size of lidocaine microemulsion with Zetasizer Nano-ZS90. With transmission electron microscope, to observe the lidocaine microemulsion morphologic. With hot plate, the antinociception effects of the drug in mice was observed. To study the Skin irritation by the method of continuous administration of the drug. RESULTS The appearance of llidocaine gel-microemulsion was transparent white gel, the shape of microemulsion was sphere, Particle size of microemulsion was less than 100 nm. Llidocaine gel-microemulsion had the significant effect of the analgesic, it caused no irritability to rabbit skin. CONCLUSION Llidocaine gel-microemulsion has good analgesic effects and safety.