Abstract: AIM　To research for new skin penetration enhancers. METHODS　N-Dodecyl-α-hydroxyl-propanamide (DHPA) and N-methyl-dodecyl-pyroglutamate (MDPG) were synthesized. The penetration enhancing ability of the compounds were evaluated in vitro using excised hairless mouse skins as bio-membrane in modified Franz-type diffusion cells. RESULTS　Data (n=6, P<0.05) showed that the enhancement ratio (ER) of DHPA and MDPG for the permeability of diclofenac sodium, caffeine in saturated aqueous-solution was 9.9, 8.7 and 7.9, 5.3 respectively compared with the control group (no enhancer present); and that of laurocapram was 8.7 and 4.6. ER of the three enhancers for vitamin E in saturated ethanol — H₂O (80∶20) solution was 3.6, 2.3 and 2.2 respectively.CONCLUSION　DHPA and MDPG can enhance the transdermal effect of diclofenac sodium, and the effect surpasses or approaches that of laurocapram at the same condition.