Objective To investigate the relationship between endothelin-1(ET-1) and cerebral vasospasm in endotoxemia rats. Methods 96 Wistar rats were randomly divided into control and experimental groups, the latter was then subdivided into 3, 6, 12, 24 and 48-h groups after the injection of lipopolysaccharide (LPS). The alteration of plasma ET-1 was detected by radioimmunoassay technique, and ET-1 immunoreactive nerve fibers in middle cerebral artery were examined with immunohistochemistry and measured with stereoscopy method. Results LPS treatment caused a significant increase of plasma ET-1 concentration at 3, 6 and 12 h after the treatment compared to that of control (P<0.05). For 24 and 48-h LPS-treated groups, the plasma ET-1 decreased and closed to the normal level (P>0.05). The ET-1 immunoreactive nerve fibers were observed in all groups, which were brown and thin line-shaped. Moreover, at 6 and 12 h after LPS treatment, the density of ET-1 immunoreactive nerve fibers on middle cerebral arteries was much higher than that of the controls (P<0.05). Conclusions Our findings suggest that, after endotoxemia, the elevated plasma ET-1 concentration, as well enhanced ET-1 immunoreactivity in cerebral arterial nerve fibers, are both involved in the development of cerebral vasospasm induced by endotoxemia.