To examine the effect of saltwort (Salicornia herbacea) on blood cholesterol and lipid metabolism, hyperlipidemia was induced in animal rats. Saltwort extract was then administered to the rats for 5 weeks, after which, blood biochemical changes were determined. Saltwort treatment resulted in a significant reduction of the levels of total cholesterol, blood triglyceride, and LDL-cholesterol. In contrast, the expression levels of HDL-cholesterol were increased at saltwort treatment group. The aspartate aminotransferase (AST: serum SGOT) value of the saltwort administration group was significantly reduced and the blood alanine aminotransferase (ALT: serum SGPT) levels decreased significantly in comparison to those in the negative control group. Degeneration of hepatic tissues due to the consumption of a high lipid diet for a long period of time was reported in the negative control group. On the other hand, in the saltwort administration group, a substantial reduction in the accumulation of lipid droplets in the cytoplasm was seen, and in addition, it was confirmed that the degeneration of hepatic tissues recovered almost to level of that of the normal control group. These data suggest that saltwort extract represents an excellent candidate for protection of rat hepatocytes from high fat diet-mediated damage.