The aim of the study was to investigate the role of endogenous peripheral and central corticotrophin-releasing factor (CRF) following lipopolysaccharide (LPS) challenge on thymic involution and apoptosis. Administration of LPS (100 μg/mouse, ip) led to thymic involution, to a decrease of CD4+CD8+ thymocyte subset, and to fragmentation of thymic DNA. Pretreatment of LPS challenged mice with intracerebroventricular α-helical CRF (a CRF antagonist) attenuated the effect of LPS however, intraventricular administered α-helical CRF failed to affect LPS response on thymus. Moreover, the effects of LPS on thymus, examined on 1, 7 and 14 days were wholly abrogated by prior administration of intraventricular CRF (10 μg/animal). The plasma corticosterone levels were found to be decreased with single dose of peripheral CRF in LPS challenged mice. These findings indicate that central endogenous CRF involved in LPS induced thymic atrophy. However, peripheral CRF offers protective effect on LPS induced thymic involution and cell apoptosis.