Phospholipase C (PLC) isozymes play significant roles in transmembrane signal transduction. PLC- 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. The exact mechanisms of this signal transduction of tissue damage and subsequent regeneration, however, were not clearly documented. This study was planned to determine the biological significance of PLC isozymes following irradiation in rat small intestine. Sprague-Dawley rats were irradiated to the entire body by a single dose of 8 Gy. The rats were divided into 5 groups according to the sacrifice days after irradiation. The expression of PLCs in each group was examined by the immunohistochemistry and immunoblotting. The histologic findings were observed using hematoxylin and eosin staining. The regenerative activity, which was estimated by mitotic count and proliferatin cell nuclear antigen (PCNA) immunostaining, was highest in Group III (5th day after irradiation). By the immunohistochemistry, the expression of PLC- 1 was higher in Group III and Group II (3rd day after irradiation), and was found in the regenerative zone of the mucosa. The expression of PLC- 1 was highest in Group I (1st day after irradiation) and was dominantly in the damaged surface epithelium. The immunostaining of PLC- 1 was negative in all groups. The results of the immunoblotting study was compatible to that of the immunohistochemical study. Group II and III showed positive bands for PLC- 1, and group I and II for PLC- 1. These results suggest that PLC- 1 plays a significant role in mucosal regeneration following irradiation. PLC- 1 may play a role in radiation - induced mucosal damage.