Malnutrition, a global health problem, impairs immune function and increases susceptibility to infection. The thymus, a primary lymphoid organ, is highly sensitive to nutritional status and is known to undergo atrophy under malnutrition. However, the temporal progression of thymic changes during malnutrition remains unclear. In this study, we used a mouse model of short-term starvation, in which dietary intake was completely withheld for 24 or 48 h to model acute fasting. The thymus of 48-h-starved mice, but not that of 24-h-starved mice, exhibited marked atrophy with a significant reduction in absolute weight. Expression levels of Th2-associated cytokines, including Il5, Il6, and Il10, were increased following 48 h of starvation, indicating polarization of Th0 cells toward a Th2-like phenotype. These phenotypic changes were not observed after 24 h of starvation. In addition, the protein level of type IV collagen was elevated in the thymus of 48-h-starved mice, proposing that dietary-restriction-induced remodeling of thymic extracellular matrix represents a novel mechanism underlying acute fasting-induced immunodeficiency.