As a new vitamin A derivative, hydroxypinacolone retinoate (HPR) has the disadvantages of poor photothermal stability and low water solubility, resulting in poor transdermal therapeutic effects. In order to improve the transdermal performance of HPR, it was combined with tocopherol acetate (VE), and HPR/VE composite nanoemulsions were prepared using high-gravity technology. The average particle size of the HPR/VE nanoemulsions (with mass fractions of HPR in the range 0.6%-3.7%) prepared under the optimized conditions of a high-gravity level of 8 and a cyclic emulsification time of 5 min was in the range 89.7-131 nm, the polydispersity index (PDI) was 0.13-0.15, and the droplets had a regular spherical morphology. There were no significant changes in the particle size, drug loading of HPR, pH and zeta potential of the HPR/VE nanoemulsions after being stored at 4 ℃ and 25 ℃ for 3 months. After centrifugation at 3000 r/min for 30 min, the particle size and PDI of the nanoemulsion had not changed significantly, and there was no crystal precipitation or emulsion stratification. Skin penetration experiments showed that the cumulative penetration amount of the HPR/VE nanoemulsion within 12 hours was 8.33 μg/cm², and the intradermal retention amount was 17.07 μg/cm². The cumulative penetration amounts within 12 hours are 2 times and 4 times that of the commercially available emulsion and the crude drug, respectively. The intradermal retention amounts are 1.5 times and 2.8 times that of the commercially available emulsion and the crude drug, respectively. The results show that the HPR/VE nanoemulsion prepared using high-gravity technology has the characteristics of small particle size, uniform distribution and regular morphology, and exhibits good storage stability and skin permeability, suggesting it has potential applications in the field of transdermal drug delivery.