AIM: To evaluate the effect of ANP on warm I/R injury in a porcine THVE model.METHODS: Miniature pigs (mini-pigs) weighing 16-24 kg were observed for 120 min after reperfusion following 120 min of THVE. The animals were divided into two groups. ANP (0.1 μg/kg per min) was administered to the ANP group (n = 7), and vehicle was administered to the control group (n = 7). Either vehicle or ANP was intravenously administered from 30 min before the THVE to the end of the experiment. Arterial blood was collected to measure AST, LDH, and TNF-α. Hepatic tissue blood flow (HTBF) was also measured. Liver specimens were harvested for p38 MAPK analysis and histological study.Those results were compared between the two groups.RESULTS: The AST and LDH levels were lower in the ANP group than in the control group; the AST levels were significantly different between the two groups (60 min: 568.7 ± 113.3 vs 321.6 ± 60.1, P = 0.038 ＜ 0.05,120 min: 673.6 ± 148.2 vs 281.1 ± 44.8, P = 0.004＜ 0.01). No significant difference was observed in the TNF-α levels between the two groups. HTBF was higher in the ANP group, but the difference was not significant.A significantly higher level of phosphorylated p38 MAPK was observed in the ANP group compared to the control group (0 min: 2.92 ± 1.1 vs 6.38 ± 1.1, P = 0.611 ＜ 0.05).Histological tissue damage was milder in the ANP group than in the control group.CONCLUSION: Our results show that ANP has a protective role in I/R injury with p38 MAPK activation in a porcine THVE model.