Abstract: The existing 3D fractured formation drilling fluid leakage model does not consider the influence of rough fracture network on drilling fluid leakage rate. In light of this, a rough surface topography equation of three-dimensional elliptical fractures was established, and the rough fracture was characterized by three parameters: fractal dimension, height amplitude, and the number of superimposed rough peaks. A three-dimensional fluid-solid coupling mechanical model of drilling fluid leakage in fractured formation was then established, and the cubic law of fluid flow in rough fractures was modified. The variation law of formation pressure and fracture width during drilling fluid leakage was studied. The examples show that the fractal dimension and height amplitude are positively correlated with drilling fluid leakage; the number of superimposed rough peaks is negatively correlated with the average fracture opening and drilling fluid leakage, while the maximum fracture opening is significantly positively correlated with drilling fluid leakage. The influence of fracture surface roughness should be fully considered when the particle size of the plugging material is selected. The plugging material should bridge the area where the opening is larger. The research results provide a theoretical basis for further understanding the leakage rule of drilling fluid in fractured formation and the inversion of fracture opening.