To investigate the protective effect of tetramethylpyrazine (TMP) on acute lung injury (ALI) in endotoxemia rats with “Collaterals Damaged by Toxic Stasis” (YuZhiLuoMai) and its mechanism of Rho/ROCK. Methods:Endotoxemia rats model in ALI with YuZhiLuoMai were established through lipolysaccharide “twohit”. Rats were randomized into 4 groups: G1 (normal control group), G2 (“twohit” group), G3 (low dosage TMP group) and G4 (high dosage TMP group). Measure the respiratory rate, lung wet/dry weight ratio, BALF PMN percentage, pulmonary MPO activity, ROCK2 mRNA expression quantity, observe and evaluate the severity of lung tissue injury. Results:Compared with the G2 rats, TMP significantly reduced respiratory rate, PMN percentage and lung wet/dry weight ratio, MPO activity and ROCK mRNA expression quantity, and reduced the pathological changes in endotoxemia rats with ALI.Conclusion:We found TMP might have better protection against ALI in endotoxemia rats with YuZhiLuoMai through inhibiting RhoA/ROCK pathway.