To examine whether sodium tanshinone II A sulfonate (STS), the main effective component of Salvia miltiorrhiza is effective in relieving the microcirculatory disturbance of small intestine by suppressing the production of reactive oxygen species (ROS) in rats with sepsis. A rat model of sepsis was induced by cecal ligation and puncture (CLP). Rats (n =40) were randomly divided into 4 groups: sham-operated group (sham, n =10), sepsis group (CLP, n =10), STS treatment group (STS, n =10) and ROS scavenger dimethylthiourea (DMTU, n =10) group. Animals in the STS group were injected with STS (1 mg/kg) for 10 min through the right external jugular vein after the CLP operation, and animals in the CLP group were given the same volume of normal saline after the CLP operation. Animals in the DMTU group were intraperitoneally injected with 5 mL/kg of 20% DMTU 1 h before CLP. The histopathologic changes in the intestinal tissues and changes of mesenteric microcirculation were observed. The levels of ROS in intestinal tissues from each group were qualitatively evaluated using a fluorescent microscope. The expressions of apoptosis signal-regulating kinase (ASK1), phosphorylated ASK1 (phospho-ASK1), p38 mitogen-activated protein kinases (p38 MAPK), phosphorylated p38 MAPK (phospho-p38 MAPK) and tissue factor (TF) were determined by Western blotting. It was shown that there were obvious microcirculatory disturbance (P < 0.05) and tissue injuries in intestinal tissues after CLP operation. The levels of ROS production, phospho-ASK1, phospho-p38 MAPK and TF were increased. Both STS and DMTU suppressed ROS, phospho-ASK1, phospho-p38 MAPK and TF production, and ameliorated the microcirculatory disturbance and tissues injury (P < 0.01). STS can ameliorate the microcirculatory disturbance of the small intestine by attenuating the production of ROS in rats with sepsis.