Objective: To investigate the alteration in heme oxygenase 1 (HO-1) activity in lung tissues from rats with severe acute pancreatitis (SAP) and its significance, as well as the influence of ulinastatin intervention. Methods: Rats were randomly divided into normal control group, SAP model group, HO-1 inducer treatment group and ulinastatin treatment group. Rats in the latter 3 group underwent retrograde cholangiopancreatic duct injection of 5% sodium taurocholate to elicit SAP model, and then rats in HO-1 inducer treatment group and ulinastatin treatment group were intravenously injected with bovine hemin or ulinastatin at 5 min after SAP model induction respectively, while those in SAP model group were injected with normal saline instead. On different time points after operation, in each group of rats, the pathological changes in the lung tissues were assessed, and the wet-to-dry lung weight ratio as well as the myeloperoxidase (MPO) activity and HO-1 expression in the lung tissues were determined. Results: Except in the normal control group, rats in all other groups exhibited obvious lung injury, which in the two treatment groups was obviously milder than that in SAP model group. Compared with normal control group, the wet-to-dry lung weight ratio, and pulmonary MPO activity and HO-1 expression in all the remaining groups were significantly elevated (all P<0.05), with a basically time increasing trend. Compared with SAP model group, the wet-to-dry lung weight ratios and pulmonary MPO activities were significantly decreased, while lung HO-1 expressions were significantly increased in the two treatment groups (all P<0.05). No statistical difference was noted in any of the parameters between the two treatment groups (all P>0.05). The correlation analysis revealed that there was a significant correlationship between HO-1 expression in the lung tissue and pulmonary MPO activity or wet-to-dry lung weight ratio in SAP rats (r=–0.79 and –0.77, both P<0.05). Conclusion: HO-1 activity is increased in rat lung tissue during SAP, and its enhancement through using HO-1 inducer can alleviate the SAP-induced acute lung injury. The protective effect of ulinastatin against SAP-induced acute lung injury may be partially associated with promotion of HO-1 activity.