The cell wall is essential for the survival and osmotic integrity of fungal cells. It is the framework to which biologically active proteins such as cell adhesion molecules and hydrolytic enzymes are attached or within which they act. Recently it was shown that mutations in α-COP, a subunit of COPI vesicle, is responsible for the thermo-sensitive osmo-fragile phenotype of fungi, such as Saccharomyces cerevisiae and Aspergillus nidulans, and suggested that α-COP may play a crucial role in translocation of protein(s) of the β-1,3-gulcan synthase complex and cell wall proteins, thus may contribute to the maintenance of cell wall integrity. In this review, we summarized the relationship between the intra-cellular protein translocation machinery, especially the α-COP of COPI vesicle, and cell wall biogenesis in fungi. We also discussed potential use of secretory mutants in basic and applied research of the fungal cell walls.