The present study was conducted to explore the protective effect of exogenous gelsolin (GSN) in mice exposed to high-dose of radiation. Changes in the levels of GSNs in peripheral blood of mice and cytoplasm of cultured human intestinal epithelial cells (HIECs) were analyzed after their exposure to different doses of (137)Cs γ-rays at a fixed dose rate. The coagulation associated indices, such as prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. Effect on radiation-mediated oxidative damage was evaluated by estimating the altered glutathione (GSH) and malondialdehyde (MDA) concentrations in the blood. The results showed that radiation induced a pronounced decrease in the pGSN blood levels. However, the cGSN levels of irradiated HIECs were increased in a dose-dependent manner. Administration of recombinant human pGSN to irradiated mice resulted in an ameliorated clotting time as indicated by the PT and the APTT indices. The treatment of mice with hpGSN enhanced the blood levels of GSH while MDA concentrations were decreased indicating an improved antioxidant status. These results suggest that GSNs might play a regulatory role in the suppression of the tissue damage induced by acute radiation exposure.