Progesterone fiber patches were fabricated using melt electrospinning technology, with a focus on screening permeation enhancers for progesterone and investigating the effects of process parameters (spinning temperature, voltage, and air pressure) on fiber morphology and fineness. In vitro transdermal experiments and air permeability tests were conducted, and comparisons were made with traditional coated patches. The results demonstrated that isopropyl myristate exhibited a significant permeation-enhancing effect on progesterone. The optimal parameters were determined as follows: spinning temperature of 140 ℃, spinning air pressure of 0.5 psi (1 psi=6894.757 Pa) and voltage of 6.0 kV, yielding fibers with an average diameter of (47.08±12.43) μm. The optimized fiber patches outperformed conventional coated patches in terms of drug release rate, transdermal efficiency, and breathability. Notably, when using porcine skin as the penetration barrier, the daily permeation flux of progesterone (30.315 μg/cm²) approached the common clinical administration requirement (35.710 μg/cm²). Furthermore, the cumulative permeation amount through murine skin reached 1.45 times that of coated patches. This study provides an effective strategy for developing novel progesterone-loaded melt-electrospun fiber patches.