The present study aimed to evaluate the effect of ulinastatin (UTI) on renal perfusion using Doppler ultrasonography in a porcine model of septic shock induced by smoking inhalation and live methicillin-resistant Staphylococcus aureus instillation. A total of 32 healthy Landrace pigs were randomly assigned into the following four groups: Sham group (SH; n=5), septic shock group (SS; n=9), septic shock treated with vancomycin (15 mg/kg) group (VAN; n=9) and septic shock treated with UTI (50,000 U/kg) + vancomycin (UTI; n=9) group. Renal perfusion was evaluated by contrast-enhanced ultrasound (CEUS) at baseline and at the end of the protocol (24 h). The spectrum of interlobar or arcuate artery was selected to calculate the corrected resistive index (cRI). Sulphur hexafluoride microbubbles were bolus injected via a venous catheter. The peak intensity (Pi) and area under curve (AUC) were calculated using a time-intensity curve. Compared with the baseline group, cRI was increased significantly at the end of the protocol, except for that in the SH group, whereas Pi decreased significantly after injury in all experimental groups but was higher in the UTI group compared with that in the SS and VAN groups (both P<0.001). Linear correlation was found between the cardiac output (CO) and Pi (R-2=0.752; P<0.001). The AUC was significantly decreased after injury in the SS and VAN groups compared with the baseline group. All parameters detected by CEUS were improved in the UTI group, and significant differences were found between the UTI and SS or VAN group (all P<0.05). In conclusion, acute renal injury, which occasionally occurs during septic shock, is accompanied with a significantly lower perfusion rate in the renal microcirculation. By contrast, UTI can significantly improve renal perfusion, which can be reliably evaluated using CEUS.