Acute pancreatitis (AP) is a serious inflammatory condition of the pancreas that can be associated with chylomicronemia syndrome (CS). Currently, no study has explored the differences between non-CS-associated AP and CS-associated AP in terms of gene expression. Transcriptomic profiles of blood samples from patients with AP were retrieved from GSE194331 (non-CS-associated) and GSE149607 (CS-associated). GSE31568 was used to examine the linkage between non-CS-associated AP and the expression of micro RNAs (miRNAs). Differentially expressed genes (DEGs) were identified, a gene regulatory network was constructed, and hub genes were defined. Subsequently, single-sample gene set enrichment analysis (ssGSEA) scores of hub genes were calculated to represent their regulatory-level activity. A total of 1851 shared DEGs were identified between non-CS-associated and CS-associated AP. Neutrophils were significantly enriched in both conditions. In non-CS-associated AP, miRNAs including hsa-miR-21, hsa-miR-146a, and hsa-miR-106a demonstrated a lower expression level as compared with the healthy control. Furthermore, the expression patterns and regulatory activities were largely opposite between non-CS-associated and CS-associated AP, with significantly lower estimated neutrophils in the latter case. In summary, we found that the regulation of neutrophils was altered in AP. There was a different gene expression pattern and lower estimated neutrophil infiltration in CS-associated AP. Whether these findings are clinically significant requires further investigation.