Dermal delivery of hydrophobic drugs by microemulsion (ME) formulations and effect from ME microstructures were studied. Anti-fungal drug, clotrimazole (CLOT), was used as the model compound. ME formulations possessing different microstructures were prepared using a ME system that contains isopropyl myristate as oil, Labrasol and Cremophor EL as surfactant and co-surfactant, and water. Permeation experiments on human cadaver skin were conducted for ME and the control formulations of different CLOT concentrations. Dermal delivery of CLOT assessed by the dermal tissue drug concentration was found to be significantly higher for MEs when compared with the control formulation, evidenced by dermal retention Enhancement Ratio (ERD) of 5.1, 2.8, and 3.0 for tested O/W, bi-continuous, and W/O MEs, respectively. The highest concentration was observed with O/W ME, suggesting the ME microstructure is an important formulation variable for enhancing dermal delivery efficiency. ME gel formulations prepared by incorporating 1.0%(w/w) of Carbopol980 showed comparable dermal CLOT concentration to MEs, but up to 2.4 fold higher than the commercial CLOT cream product, Lotrimin®. Furthermore, Fluorescein Isothiocynate (FITC), used as a model compound for highly hydrophobic drugs, was also studied for dermal delivery by MEs, and results show consistent ME microstructure effect, suggested by significantly higher FITC concentrations in all skin layers, SC, viable epidermis, and dermis, from O/W ME over bi-continuous and W/O MEs.