Fabrication of three-dimensional (3D) fibrin scaffolds with tightly controllable pore sizes and interconnections has been investigated. The scaffolds were produced using a combination of two-photon polymerization (2PP) and micromolding techniques. Master structures were fabricated by 2PP and regenerated in fibrin by a two-step microreplication procedure. Scanning electron and optical microscopy observations showed that the fibrin scaffolds exhibited a highly porous and interconnected structure. Seeding of endothelial cells in fibrin scaffolds resulted in their directed lining and spreading within network of microreplicated pores, whereas encapsulation of endothelial cells in fibrin gel blocks led to their chaotic and irregular distribution within constructs. These results demonstrate that the 2PP-micromolding technique is suitable for fabrication of complex 3D structures from natural proteins for tissue engineering applications.