Yiqifumai is a traditional Chinese medicine compound preparation used for the treatment of various vascular diseases in China. However, little is known regarding its role in microcirculation. The present study investigated the effect of pretreatment of Yiqifumai on rat mesentery microcirculatory disturbance induced by LPS. Male Wistar rats were continuously infused with LPS (5 mg kg(-1) h(-1)). The parameters evaluated included diameter of and red blood cell velocity in venules, leukocyte adhesion to venular wall, dihydrorhodamine 123 (DHR) fluorescence in the venular walls, fluorescein isothiocyanate-albumin leakage, and mast cell degranulation, which were observed by an inverted intravital microscope. CD11b/CD18 expression on neutrophils was examined using flow cytometry. In some rats, Yiqifumai (5, 30, or 80 mg kg(-1)) was given in one shot 10 min before LPS infusion. After infusion of LIPS, the number of leukocytes adherent to venular wall, the intensity of DHR fluorescence in the venular walls, albumin leakage from venules, and degranulated mast cells were significantly increased, whereas the red blood cell velocity in venule was decreased. Pretreatment with high-dose Yiqifumai (80 mg kg(-1)) significantly reduced the number of adherent leukocytes, the intensity of DHR fluorescence, degranulation of mast cell, albumin leakage, and the expression of CD11b/CD18, whereas the Yiqifumai of medium dose (30 mg kg(-1)) only inhibited leukocyte adhesion to the venular wall. The results suggested that pretreatment with Yiqifumai attenuated microcirculatory disturbance induced by LIPS. This effect may be associated with Yiqifumai's inhibition effect on reactive oxygen species production, leukocyte adhesion, and mast cell degranulation.