Abstract: A circular microfluidic device was developed using a microfluidic approach combined with numerical simulation and experimental validation to successfully construct and regulate the performance of luteolin-loaded liposomes (Lut Lips). The effects of operational parameters, including total flow rate and flow rate ratio, on the mixing performance of the microfluidic device were systematically investigated, as well as the influence of formulation variables, including phospholipid-to-cholesterol ratio and luteolin concentration, on liposome particle size and luteolin encapsulation efficiency.Under optimized conditions, Lut Lips with a particle size of 220.5 nm and an encapsulation efficiency (EE) of 64.72% were obtained, exhibiting excellent monodispersity with a polydispersity index (PDI) of 0.037. Human immortalized keratinocytes (HaCaT) were used as an in vitro uptake model and co-incubated with fluorescently labeled liposomal nanoparticles (Lips), demonstrating that the delivery system effectively penetrated the cellular membrane barrier and achieved intracellular drug delivery.The findings of this study confirm the feasibility of liposomal nanoparticles as a novel drug delivery system for luteolin and provide new insights and experimental evidence for the design of delivery systems for luteolin and other lipophilic drugs.