Objective To investigate the skin stimulation effect of essential oils from Ligusticum chuanxiong Hort. Methods HaCaT cells were cultured in vitro. Using MTT and ELISA methods, we examined the effect of the essential oil (different concentrations) on HaCaT cell proliferation and prostaglandin E₂ (PGE₂) levels in culture supernatants of HaCaT cells, and the results were compared with those of oleic acid, a classic permeation enhancer. The cumulative skin stimulation effect was determined by visual scoring in guinea pigs and the histological changes were determined by light microscopy.Results The HaCaT cell viabilities of the 0.005%, 0.015%, and 0.025% essential oil groups were 1.79-, 1.65-, and 1.48-fold that of the 0.005% oleic acid group, respectively, and there was no significant difference between the 0.05% essential oil group and 0.005% oleic acid group. The 0.005%, 0.015%, 0.025%, and 0.05% essential oil influenced the supernatant PGE₂ levels by (0.99±0.08)%,(1.63±0.09)%,(0.98±0.09)%, and (0.04±0.01)%, respectively, which were all significantly lower than the influence of 0.005% oleic acid (\[4.23±0.68\]%, P<0.05). Only slight erythema was observed after continuous administration the essential oil (different concentrations) for 7 days, with no edema or skin uplift, and the erythema caused by 15% essential oil was lower than that caused by 5% oleic acid.Only 15% essential oil exhibited the mechanical injury of the stratum corneum. And 5% oleic acid group showed stripped and lost stratum corneum over large areas. Conclusion Chuanxiong oil is less cytotoxic and less stimulating to the skin compared with oleic acid, and may become an excellent skin permeation enhancer.