Objective: To find a more effective method of topical transdermal delivery of curcumin. Methods: We prepared curcumin carbopol(CRB) 974P and hydroxypropylcellulose(HPC) gel formulations containing menthol or Azone as permeation enhancers. In this study, negative mode electrospray ionization and a triple quadruple LC/MS/MS instrument operated in multiple reaction mode was used for curcumin detection. The assay was linear over a concentration range of 10 ng/mL to 400 ng/mL for curcumin(average R2= 0.997 2). Excised nude mouse dorsal side skin was used in an in vitro skin permeation study performed using the method of Franz. Results: Our results showed that all of the topical gel formulations we developed were free from skin irritation. The percutaneous flux and enhancement ratio of curcumin across nude mouse epidermis were enhanced markedly by the addition of menthol or Azone to both types of gel formulations. We found that the HPC gels containing quantities of Azone showed an enhanced permeation effect as compared to gels containing menthol. In the case of HPC gels containing Azone, the increase in permeability was significant(P<0.05) as compared to the gels containing menthol. Conclusion: Azone shows a significantly more remarkable permeation effect than menthol. As such, this novel delivery strategy offers significant promise and is worthy of further exploration in attempts to enhance the medicinal application of curcumin. Objective: To find a more effective method of topical transdermal delivery of curcumin. Methods: We prepared curcumin carbopol (CRB) 974P and hydroxypropylcellulose (HPC) gel formulations containing menthol or Azone as permeation enhancers. In this study, negative mode electrospray ionization and a Triple quadruple LC / MS / MS instrument operated in multiple reaction mode was used for curcumin detection. The assay was linear over a concentration range of 10 ng / mL to 400 ng / mL for curcumin (average R2 = 0.997 2). Excised nude mouse dorsal side skin was used in an in vitro skin permeation study performed using the method of Franz. Results: Our results showed that all of the topical gel formulations we developed were from skin irritation. The percutaneous flux and enhancement ratio of curcumin across nude mouse epidermis were enhanced markedly by the addition of menthol or Azone to both types of gel formulations. We found that the HPC gels containing quantities of Azone showed an enhanced p ermeation effect as compared to gels containing menthol. In the case of HPC gels containing menthol. the increase in permeability was significant (P <0.05) as compared to the gels containing menthol. Conclusion: Azone shows a significantly more remarkable permeation effect than menthol. As such, this novel delivery strategy offers significant promise and is worthy of further exploration in attempts to enhance the medicinal application of curcumin.