The aim of the present study was to investigate the effects of Toll?like receptor (TLR) 9 and CpG oligodeoxynucleotide (CpG?ODN)1826 on sodium taurocholate?induced acute pancreatitis (AP) rats at different time points. Pathological examination indicated that the severity of pancreatic tissue damage following AP increased with time. Additionally, TLR9 protein levels were upregulated after AP, and were higher at 6?h compared with at 3?h. Subsequently, the TLR9 protein levels were downregulated at 12?h, but remained higher than the control group. In rats subjected to AP, tumor necrosis factor (TNF?α protein expression levels and serum amylase?(AMS) in the serum were increased until 12?h. The expression level of TNF?α protein in the AP 12?h group was higher than that in the AP 3 and 6?h groups. In addition, following CpG?ODN1826 administration, the morphology of pancreatic tissue appeared worse compared with that in the AP only groups. Furthermore, CpG?ODN1826 administration induced an increase in TLR9 expression levels compared with the AP alone group at 0, 3, 6 and 12?h. TNF?α in the CpG?+?AP 12?h group was upregulated compared with that in the CpG?+?AP 3 and 6?h groups; however, no change was observed between 3 and 6?h. Thus, these data indicate that CpG?ODN1826 aggravates sodium taurocholate?induced pancreas damage in rats.