The aim of this prospective study was to assess the usefulness of pretreatment with ulinastatin to reduce cerebral ischemia/reperfusion injury during carotid endarterectomy under general anesthesia. Forty patients were randomized into the ulinastatin group and the control group. Patients in the ulinastatin group received a 500000 U dose of ulinastatin immediately before anesthesia induction. Participants in the control group were administered with equal normal saline. Blood samples were drawn from the ipsilateral jugular bulb before skin incision, at 15 min after clamping and 15 min after declamping individually, and daily postoperatively for 3 d for malondialdehyde(MDA),tumor necrosis factor α(TNF-α) determination, before skin incision, at 15 min after clamping and 15 min after declamping for blood gas analysis, and before skin incision, daily postoperatively for 3 d for neuron-specific enolase(NSE) determination. Blood samples were drawn from the artery before skin incision, at 15 min after clamping and15 min after declamping individually for blood gas analysis. Compared with the control group, the ulinastatin group had the lower concentration of TNF-α at every time point(P0.05), but the higher cerebral arteriovenous oxygen content difference at 15 min after declamping(P0.05), and the decreased ICU stay of 38.7%(27.1±15.7 h vs.44.1±29.6 h, P0.05). There were no differences between the ulinastatin group and the control group in MDA and NSE(P0.05). Pretreatment with ulinastatin was useful to prevent inflammatory response and to improve cerebral oxygen metabolism and outcomes after carotid endarterectomy.