Liquid intraurethral prostaglandin E1 (PGE1) delivery system was developed using self-microemulsifying drug delivery system (SMEDDS). For this, pseudo-ternary phase diagrams were constructed and characterized. The viscosity of optimized formulation was increased gradually upon the addition of water and it was decreased from the water contents over 40%. With excessive mass of water, the present system transformed to a free flowing microemulsion. These results demonstrate that the present liquid PGE1 SMEDDS formulation might stay in the urethra as a viscous sol or gel state with contacting the moisture of urethra and easily eliminated by urination. Draize test and long-term stability study revealed that the present system would be safe and PGE1 would be stable for more than one year at 4 degrees C, respectively. In the feline animal model, SMEDDS formulation was as effective as PGE1 intracavernosal injections in terms of ICP (intracavernosal pressure), penile length increment, and erection sustaining time was more elongated than PGE1 injections. Therefore, SMEDDS was considered as a promising PGE1 intraurethral liquid formulation for erectile dysfunction treatment.