Integrated traditional Chinese medicine (ITCM) is known to improve health in patients with acute pancreatitis (AP); however, the molecular mechanisms underlying this effect are unknown. AP is associated with the expression of PRSS1 and SPINK1. Thus, the present study aimed to investigate whether ITCM was able to ameliorate AP by regulating the expression levels of protein, serine 1 (PRSS1) and serine peptidase inhibitor, Kazal type 1 (SPINK1). A total of 100 AP patients were divided at random into two groups. The treatment group were treated externally with a herbal ITCM preparation, while the control group received a routine placebo treatment. The mRNA and protein expression levels of PRSS1 and SPINK1 were subsequently compared between the two groups. The results revealed that the health of the patients who had received ITCM improved significantly when compared with the control group patients (P<0.05). In addition, the expression levels of PRSS1 and SPINK1 were found to be lower in the treatment group when compared with the control group (P<0.05). Therefore, ITCM exhibited a significant therapeutic effect on AP and produced no side effects since the treatment was applied externally. ITCM may ameliorate AP by downregulating the expression of PRSS1 and SPINK1; thus, should be considered as a potential therapy for the development of drugs against AP.