Abstract: In order to explore the effect of jugular vein injection of lipopolysaccharide on blood routine, serum biochemical and oxidative stress indexes in sheep and its potential mechanism, 8 healthy Dorper sheep with similar birth time and normal growth and development were selected in the experiment, which were injected with LPS in the jugular vein of 0.8 μg/kg body weight respectively. And before the injection of LPS and 0.5, 2, 4, and 6 hours after the injection of LPS, blood was collected to detect blood routine indexes（leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils）, serum biochemical indexes（immunoglobulin G IgG, immunoglobulin A IgA, immunoglobulin M IgM, total protein TP, glucose GLU, aspartate aminotransferase AST, alanine aminotransferase ALT, albumin ALB） and oxidative stress indexes（total antioxidant capacity T-AOC, superoxide dismutase SOD, glutathione peroxidase GSH-Px, malondialdehyde MDA）. The results showed that in the blood routine index, the number of blood leukocytes decreased from（11.529±0.928）×10~9/L before injection to（3.446±0.397）×10~9/L at 0.5 hours after LPS injection, and the difference was significant（P＜0.05）; the number of leukocytes at 2, 4 and 6 hours after LPS injection was significantly lower than that before injection（P＜0.05）. The numbers of neutrophils, lymphocytes, monocytes, eosinophils and basophils after LPS injection were also significantly lower than those before injection（P＜0.05）. In serum biochemical indexes, 4 hours after LPS injection, the contents of IgG, IgA, and TP decreased significantly while the content of IgM increased significantly（P＜0.05）; 2 hours after LPS injection, GLU content reached the highest point, and there was a significant difference before injection（P＜0.05）; ALB content, AST and ALT activities had no significant changes before and after injection（P＞0.05）. In the oxidative stress indexes, 4 hours after LPS injection, the activities of T-AOC, SOD and GSH-Px were significantly decreased（P＜0.05）, and T-AOC decreased from（12.01±0.11）U/mL before injection to（9.64±0.13）U/mL（P＜0.05）, and the MDA content was significantly higher than that before injection（P＜0.05）. The results suggested that LPS could activate the immune system, leading to oxidative stress and causing a systemic inflammatory response in sheep.