Ulcerative colitis (UC) is a recurrent, chronic intestinal disease that is currently incurable. Its pathogenesis remains to be further understood. Therefore, seeking new biomarkers and potential drug targets is urgent for the effective treatment of UC. In this study, the gene expression profile GSE38713 was obtained from the GEO (Gene Expression Omnibus) database. Data normalisation and screening of the differentially expressed genes (DEGs) were conducted using R software, and gene ontology (GO) enrichment was performed using Metascape online tools. The PubMed database was used to screen new genes that have not been reported, and SERPINA3 was selected. The correlation between SERPINA3 and other inflammatory factors was analysed by Spearman correlation analysis. Finally, colitis model mice and an in-vitro model were established to validate the function of the SERPINA3 gene. SERPINA3 gene expression was markedly increased in UC patient samples, colitis models and in-vitro models and showed an association with other inflammatory factors. ROC analysis indicated that SERPINA3 could represent a potential biomarker of active UC. Additionally, silencing SERPINA3 in an in-vitro intestinal epithelial inflammatory model significantly decreased the mRNA level of inflammatory factors. This study provides supportive evidence that SERPINA3 may act as a key biomarker and potential drug target in UC treatment.